[Show abstract][Hide abstract] ABSTRACT: Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.
Modern Pathology 02/2012; 25(6):877-84. DOI:10.1038/modpathol.2011.220 · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine matrix metalloproteinase-2 and survivin expressions in endometrial cancers, their relation to clinical and histologic parameters and to investigate any difference in the expression of these markers between endometrioid and nonendometrioid cancers.
Ninety-five patients with endometrial cancer, were included. Matrix metalloproteinase-2 and survivin expressions were analyzed immunohistochemically from paraffin-embedded tissues by using specific monoclonal antibodies.
Survivin nuclear expression was higher in endometrioid cancer as compared to nonendometrioid cancer (p=0.040), but there was no difference for cytoplasmic survivin and matrix metalloproteinase-2 expressions between type I and type II carcinomas. Survivin cytoplasmic staining was significantly lower in patients with deep myometrial invasion (p=0.038). Nuclear expression of survivin is decreased in histologic grade 3 tumors compared to grade 1 and 2 tumors (p=0.013), but there is no difference between grade 1 and 2. We did not find any statistically significant difference between survivin or matrix metalloproteinase-2 expressions and survival.
Survivin and matrix metalloproteinase-2 are present in endometrioid and nonendometrioid cancers. Grade 1 and 2 tumors and carcinomas having myometrial invasion less than 50% have higher survivin expression. These results supports that, survivin may play an important role in early stage tumors and early phases of tumor development. We did not find any association between matrix metalloproteinase-2 expression and classical prognostic factors in endometrial cancer and both proteins were not associated with survival.
[Show abstract][Hide abstract] ABSTRACT: To evaluate follicle loss in ovarian tissue after laparoscopic excision by the stripping technique in endometriomas versus benign nonendometriotic ovarian cysts.
Cystectomy samples obtained from 127 ovaries from 104 patients (mean age, 29.05 ± 05 years; range, 19-40 years) by laparoscopic excision (61 endometriomas and 66 benign nonendometriotic cysts) were evaluated for follicle loss. The samples including normal ovarian tissue were graded on a semiquantitative scale from 0 to 4, where 0 was complete absence of follicles and 4 was the pattern of primary and secondary follicles seen in a normal ovary. The results from endometriomas were compared with those from nonendometriotic cysts.
There were no differences in mean tissue thickness, or number of primordial, primary, or secondary follicles between the endometriomas and the nonendometriotic cysts (P > 0.05). Ovarian cortex was detected in 92% and 82% of the endometriomas and nonendometriotic samples, respectively, (P = 0.081). Semiquantitative scoring of ovarian tissue was significantly higher in endometriomas (1.64 ± 1.35 versus 1.11 ± 1.22, P = 0.022).
In up to 92% of the cystectomy samples, normal ovarian tissue was found adjacent to the benign cyst; however, functional follicle loss was slightly, but significantly, higher in the endometriomas.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 06/2011; 114(2):124-7. DOI:10.1016/j.ijgo.2011.04.002 · 1.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10(- 8) mol/L), progesterone (10(-7) mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.
[Show abstract][Hide abstract] ABSTRACT: The role of RNA-binding proteins in cancer biology is recognized increasingly. The nucleocytoplasmic shuttling and AU-rich RNA-binding protein HuR stabilizes several cancer-related target mRNAs. The proto-oncogene c-fms, whose 3'untranslated region (3'UTR) is not AU-rich, is associated with poor prognosis in breast cancer. Using a large breast-cancer tissue array (N=670), we found nuclear HuR expression to be associated with nodal metastasis and independently with poor survival (P=0.03, RR 1.45), as well as to be co-expressed with c-fms in the breast tumors (P=0.0007). We described c-fms mRNA as a direct target of HuR in vivo, and that HuR bound specifically to a 69-nt region containing 'CUU' motifs in 3'UTR c-fms RNA. Overexpressing or silencing HuR significantly up- or down-regulated c-fms RNA expression, respectively. We also found that known glucocorticoid stimulation of c-fms RNA and protein is largely dependent on the presence of HuR. HuR, by binding to the 69-nt wild type, but not mutant, c-fms sequence can regulate reporter gene expression post-transcriptionally. We are the first to describe that HuR can regulate gene expression by binding non-AU-rich sequences in 3'UTR c-fms RNA. Collectively, our findings suggest that HuR plays a supportive role for c-fms in breast cancer progression by binding a 69-nt element in its 3'UTR, thus regulating its expression.
[Show abstract][Hide abstract] ABSTRACT: To define the long-term effects of GnRH antagonist, GnRH agonist, and estrogen plus progesterone treatments on apoptosis and apoptosis-related gene expressions, including bcl2, bax, and cyt c in rat ovary.
Prospective placebo-controlled experimental study.
Obstetrics and Gynecology and Medical Biology and Genetics university departments.
Forty female wistar rats that were 3 to 4 months of age.
Forty rats were randomly divided into 4 groups of 10 each. In group 1 (control) each rat received normal saline as placebo by gastric lavage. In group 2 (GnRH agonist) 1 mg/kg leuprolide acetate in depot form was given for 30 days. In group 3 (GnRH antagonist) each animal received 0.1 mg/kg cetrorelix every 2 days. In group 4 (estrogen plus progesterone) 0.5 mg/kg estradiol valerate and norethisterone enantate in depot form was given every 30 days. After 60 days, the animals were killed.
Assessment of morphology, histology of ovaries, determination of the number of apoptotic cells, and analysis of apoptosis-related gene expression of bcl2, bax, and cyt c in the rat ovaries.
Long-term GnRH antagonist treatment significantly increased bax gene expression, but the ratio of bcl2:bax gene expression was constant compared with control group. The GnRH agonist treatment significantly increased cyt c gene expression, and estrogen plus progesterone treatment significantly decreased bcl 2 and significantly increased cyt c expressions. In the estrogen plus progesterone group, ovaries were cystic and larger than in the other groups. There was no significant morphologic change between the other groups.
Long-term administration of GnRH agonist, GnRH antagonist, and estrogen plus progesterone can modulate the apoptosis-related genes in rat ovary. Although GnRH antagonist treatment does not influence apoptosis, GnRH antagonist and estrogen plus progesterone treatments seem to influence apoptosis in rat the ovary. Further clinical studies focusing on the effect of these agents on apoptosis-related genes could be performed.
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression and localization of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in women with and without endometriosis.
Comparative immunohistochemical study.
Academic medical center.
Ectopic (n = 24) and homologous eutopic endometrium (n = 24) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of IL-8 and MCP-1.
Tissue sections were immunostained with antihuman IL-8 and MCP-1 antibodies.
Microscopic evaluation to assess the presence and localization of IL-8 and MCP-1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with endometriosis and comparison with normal endometrium.
In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples. Epithelial MCP-1 expression was similar in both proliferative and secretory phases. Proliferative phase samples showed higher epithelial IL-8 and MCP-1 expressions in eutopic endometrium of women with endometriosis compared with that of normal women. Immunoreactivities of both chemokines were significantly increased in the epithelial cells of ectopic endometrial tissues compared with those of normal endometrium.
These findings suggest that IL-8 and MCP-1 may be involved in the pathogenesis of endometriosis.
Fertility and sterility 04/2008; 91(3):687-93. DOI:10.1016/j.fertnstert.2007.12.067 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the immunohistochemical expression of cell proliferation and apoptosis markers in the ovaries and uterus of tamoxifen-treated rats. Twelve rats (150-200 g) were divided into two equal groups. The study group received daily intraperitoneal injections of tamoxifen dissolved in 5% dimethyl sulfoxide (n= 6). The control group received only the vehicle (n= 6). The rats were sacrificed at the 20th day of injection and were perfused. The ovaries and uterus of the rats were extracted. The sections were immunohistochemically stained with cell proliferation marker Ki-67 and the apoptosis markers PTEN and CD95. The expressions of the markers were quantified by a semiquantitative H-score method in myometrium, endometrial glands, ovarian surface epithelium, ovarian follicles, corpus luteum, and ovarian stroma separately. The mean H-scores of CD95 and PTEN obtained from myometrium, glandular endometrium, ovarian surface epithelium, ovarian follicles, corpus luteum, and ovarian stroma did not show significant difference between the study and the control groups. Proliferative index (Ki-67) of endometrial glands was significantly higher in the study group than in the control group (P < 0.05). In addition, proliferative index (Ki-67) of corpus luteum was significantly higher in the study group than in the control group (P < 0.05). Tamoxifen treatment has a potential to stimulate the cell proliferation of endometrial glands and corpus luteum in tamoxifen-treated rats. Apoptosis markers of PTEN and CD95 did not demonstrate significant difference after the tamoxifen treatment.
International Journal of Gynecological Cancer 01/2008; 18(1):141-5. DOI:10.1111/j.1525-1438.2007.00956.x · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 03/2007; 15(1):31-7. DOI:10.1097/01.pai.0000201808.35931.78 · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endometrial glandular dysplasia (EmGD) is a newly defined entity that is commonly and specifically associated with serous endometrial intraepithelial carcinoma and uterine papillary serous carcinoma (UPSC). Endometrial glandular dysplasia has been proposed as a true precancerous lesion of UPSC based on our recent studies showing morphological and molecular linkages between these 2 lesions. The present report is to examine if EmGD occurs before UPSC development and to define the period from the occurrence of EmGD to a full-blown UPSC by studying their clinicopathologic features in a retrospective setting. A total of 250 UPSC and 258 benign cases were used as initial study source. To identify if EmGD existed before the development of UPSC, we blindly reviewed all available endometrial biopsies from a period of 3 months or earlier before hysterectomies. These included an available pool of 27 biopsy specimens from UPSC group and 29 samples from benign control group. Any endometrial abnormalities, which morphologically qualified as EmGD as defined previously in preceding biopsies were recorded. Among all endometrial biopsies before hysterectomies, we morphologically identified a total of 10 EmGD cases; 9 (33%) of 27 were from UPSC group and 1 (3.5%) of 29 were from benign control group. All 10 morphologically diagnosed EmGD cases showed a high p53 staining score (>/=5) except 1 noncontributory from UPSC group and 1 from the benign control group with a score of 0. A high MIB-1 index score was seen in all EmGD cases, whereas low index was found in morphologically benign biopsies. The main purpose of this study is to report these retrospectively identified EmGD cases. The period from identifying EmGD to the presence of either a serous endometrial intraepithelial carcinoma or a full-blown UPSC ranged from 16 to 98 months with an average of 33 months. We conclude that occurrence of EmGD precedes the development of UPSC. The findings support our recently proposed UPSC development model, in which EmGD is likely to be a precursor lesion of UPSC. Further studies are needed to address issues in regard to molecular and cellular mechanisms, reversibility, risk of UPSC development, and clinical management of EmGD.
International Journal of Gynecological Pathology 02/2007; 26(1):38-52. DOI:10.1097/01.pgp.0000228138.56222.4e · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The recognition of morphologically identifiable lesions which may confer an increased risk for subsequent development of an invasive malignancy offers an opportunity to investigate and better understand the molecular-genetic etiopathogenesis of the well-developed tumor, and potentially, to administer a therapeutic intervention before its development. In contrast to uterine endometrioid and serous carcinomas, very little is known about the potential precursor lesions of endometrial clear cell carcinoma (ECCC). In our routine practice, we have noted the presence of a spectrum of atypical glandular changes in the endometria adjacent to ECCC or endometrial carcinomas with a clear cell component, which on the basis of current criteria, would not qualify for any specific designation. We hypothesize that these lesions represent the earliest morphologically recognizable precursor lesions of ECCC and systematically characterize their clinicopathologic features herein. Thirty archived cases of pure ECCC (n=14) or mixed endometrial carcinomas with a >10% clear cell component (n=16) were retrieved and the "normal" endometria adjacent to the malignancies were evaluated in detail. Thirty-eight benign uteri and 30 uteri with classic endometrial endometrioid carcinoma (EEC) served as controls. All cases were reviewed in a blinded fashion. Putative precursor lesions (PPL) were searched for and identified microscopically. The lesions were typically isolated glands or surface epithelium (within an otherwise normal endometrial region) that displayed cytoplasmic clarity and/or eosinophilia with varying degrees of nuclear atypia. Twenty-seven (90%) of the 30 cases had at least 1 PPL. In contrast, PPL were identified neither in the benign uteri nor in endometrioid carcinoma control groups (P<0.001). A total of 67 foci of PPL were identified in the 27 cases with an average of 2.5 foci per case. The immunohistochemical expression of p53, mib-1, estrogen receptor (ERs), and progesterone receptor in the benign endometria, ECCC, and the PPL were evaluated on all 27 cases. The mean p53 scores for the benign endometria, PPL, and ECCC were 0, 4.5, and 6.2, respectively. Parallel values for mib-1 were 15%, 45%, and 63%. ER/progesterone receptor indices for benign endometria, PPL, and carcinoma were 90/80, 21.52/4.61, and 11/4, respectively. The PPL described herein have a morphologic and immunophenotypic profile which seems to be distinct from both the benign endometria in which they reside and the adjacent areas of ECCC. The high frequency of association of these lesions with ECCC, their frequent occurrence as isolated lesions within otherwise "benign-appearing" endometria, and their continuous spectrum of nuclear atypia from minimum (grade 1, cytologic atypia falls short of ECCC cells) to maximum (grade 3, cytologically identical to ECCC cells), argues in favor of our hypothesis that these may represent precursor lesions of ECCC. Further studies are required to conclusively define the nature of these lesions. However, such studies can only be performed if diagnostic surgical pathologists recognize, highlight, and segregate these lesions for further analysis.
American Journal of Surgical Pathology 01/2007; 30(12):1519-30. DOI:10.1097/01.pas.0000213296.88778.db · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 in adenomyosis.
Comparative immunohistochemical study.
Academic medical center.
Thirty women who had undergone hysterectomy and were proved histopathologically to have adenomyosis, and 27 women without adenomyosis who had a hysterectomy for nonendometrial pathology such as leiomyomata or benign ovarian cysts.
Tissue sections were immunostained with murine monoclonal anti-human CXCR1 and CXCR2 antibodies.
Microscopic evaluation to assess the presence and localization of CXCR1 and CXCR2 throughout the menstrual cycle in both eutopic endometrial and adenomyotic tissues of women with adenomyosis and compare it with normal endometrium.
In eutopic endometrium of women with adenomyosis, proliferative phase samples showed higher epithelial CXCR1 and CXCR2 staining intensity compared with proliferative phase samples of normal endometrium. Adenomyosis foci expressed higher epithelial CXCR1 compared with the homologous eutopic endometrium and normal endometrium. On the other hand, adenomyosis foci and the homologous eutopic endometrium showed similar epithelial CXCR2 staining intensity, and this expression was higher than the normal controls.
Intrinsic abnormalities concerning IL-8 and its receptor system may be present in the eutopic endometrium of women affected by adenomyosis. These findings suggest that IL-8 receptors may be involved in the pathogenesis and/or pathophysiology of adenomyosis.
Fertility and sterility 04/2006; 85(3):714-20. DOI:10.1016/j.fertnstert.2005.08.053 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the inflammatory nature of adenomyosis, we aimed to investigate the expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) by immunohistochemistry to determine their putative role in pathophysiology of adenomyosis.
Adenomyosis samples, with their eutopic endometrium, were collected from 30 women undergoing hysterectomy. Endometrium from 27 women without adenomyosis were also collected as a control group. Samples were grouped according to the menstrual cycle phase and examined by immunohistochemistry for IL-8 and MCP-1.
In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples (P = 0.01), and we observed a trend for an increased epithelial MCP-1 expression in the secretory phase samples compared with the proliferative phase samples (P = 0.07). Endometrial samples of women with adenomyosis did not show the same cyclic variation. In the secretory phase, eutopic endometrium of women with adenomyosis expressed lower levels of epithelial IL-8 and MCP-1 compared with normal endometrium (P < 0.05). The expression of epithelial IL-8 and MCP-1 was higher in the adenomyosis foci than the eutopic endometrium (P < 0.05).
These findings may indicate that an intrinsic abnormality of inflammatory response may be present in eutopic endometrium of women with adenomyosis, and IL-8 and MCP-1 may contribute to the pathophysiology of adenomyosis.
Human Reproduction 10/2005; 20(10):2958-63. DOI:10.1093/humrep/dei154 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is believed that ovarian endometriosis may be generated by a celomic metaplastic process from existing epithelium in the ovary. However, no morphologic evidence of metaplastic process has been described. In this study, we intended to identify the earliest morphologic changes of endometriosis within the ovary to examine if evidence of metaplasia exists. Included in this study were 110 ovarian endometriosis cases and 30 benign ovaries without endometriosis but with ovarian epithelial inclusions (OEIs). Among the 110 well-established ovarian endometriosis cases, 34 cases showed areas of initial endometriosis (IE), which is defined as lesions showing direct transitions from normal-looking ovarian tissue to areas of minimal formation of endometriosis and/or to areas of full-blown endometriosis. We further divided IE into two types: type I IE was present on the ovarian surface, which was associated with ovarian surface epithelia; type II was located within the ovarian cortex, which was associated with OEIs. Sections containing IE, OEIs, and well-formed endometriosis were subject to CD10 and aromatase immunostaining. In IE lesions, the number of CD10-positive cells were significantly higher than the number of that in OEIs, but lower than that of well-formed endometriosis areas (p < 0.05). Aromatase expression was detected in both epithelial and stromal components of the IE lesions, indicating that estrogen local production may be involved in this initial process of endometriosis. Microvessel density was higher in IE lesions than in areas of OEI (p < 0.05). Based on the morphologic characteristics of IE, we believe that IE represent a spectrum of the earliest morphologic changes of endometriosis identifiable by routine microscopy. The morphologic transitions from ovarian surface epithelium or OEI to IE lesions provide direct metaplastic evidence for the pathogenesis of ovarian endometriosis. This metaplastic process may not only involve the ovarian epithelial cells, but also stromal components. Local production of estrogen, probably in high-levels, may be related to the initial process of endometriosis, although detailed mechanisms remain to be clarified.
International Journal of Gynecological Pathology 04/2005; 24(2):164-72. DOI:10.1097/01.RCT.0000157091.37057.B4 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the etiology of endometriosis is not well understood, chemokines and their receptors are believed to play a role in its pathogenesis. Therefore, we aimed to investigate the expression and localization of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 in eutopic and ectopic endometrial tissues of women with endometriosis, and in endometrium of women without endometriosis.
Ectopic (n = 27) and homologous eutopic endometrium (n = 25) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of CXCR1 and CXCR2.
In normal endometrium, epithelial CXCR1 and CXCR2 immunostaining intensities were similar in the proliferative and secretory phase. Stromal CXCR1 expression was less then epithelial expression and did not show cyclical difference. No stromal CXCR2 expression was observed. In eutopic endometrium of women with endometriosis compared to endometrium of women without endometriosis, there was a significant increase in both proliferative and secretory phases for epithelial CXCR2 expression, and in proliferative phase for CXCR1 expression (P < 0.05). Both receptor immunoreactivities were significantly increased in the epithelial cells of ectopic endometrial tissues compared to that of normal endometrium (P < 0.05).
These findings suggest that IL-8 and its receptors may be involved in the pathogenesis of endometriosis.
Human Reproduction 04/2005; 20(3):794-801. DOI:10.1093/humrep/deh675 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A proportion of cervical squamous intraepithelial lesions encountered in surgical pathology practice contain both metaplastic features and some degree of atypia [so-called eosinophilic dysplasia (ED)] that defy classification according to established criteria. To elucidate the nature of these lesions, we compared 44 cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and 10 squamous metaplasias using a panel of biomarkers and human papillomavirus (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively abundant eosinophilic cytoplasm and distinct cell borders compared with conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic ratio; and 4) focal dysplastic nuclei showing nuclear enlargement, hyperchromasia, variable nuclear membrane irregularities, and appreciable nucleoli. Expression of p16 (p16), MIB-1 (Ki-67) labeling index, and HPV DNA detection and typing were performed on each case. The majority of EDs showed more than three atypical cells in an entire lesion but lack of apparent features of HSIL. It was common to find neighboring cervical squamous metaplasia and/or conventional SILs (either HSIL or low-grade squamous intraepithelial lesion [LSIL]). Among the 44 cases, 18 (45%) ED lesions were found to be associated with HSIL, 15 (34%) with LSIL or condylomatous lesions, and 13 (30%) EDs were seen without any SILs in the entire specimens. Area of benign squamous metaplasia was found in all ED cases. High levels of p16 and MIB-1 expression were seen in 41 (93%) of 44 ED cases with degrees of immunoreactivity closely resembling those seen with HSIL. Of 16 EDs tested, 13 (81%) were positive for HPV DNAs. Among 10 HPV-positive cases subtyped, 9 (90%) cases contained intermediate- and/or high-risk HPVs and 1 case contained a novel HPV. In the follow-up of pure ED cases, the majority showed presence of dysplastic lesions of either HSIL or LSIL on either loop electric excision procedures or Papanicolaou test samples after a 6- to 10-week period. Therefore, ED represents an unrecognized and potentially clinically significant subgroup of cervical intraepithelial lesions. Based on the unique histologic appearance of ED, its association in some cases with HSIL, the overall immunohistochemical findings, frequent association of ED with intermediate- and/or high-risk HPV infection, and limited follow-up data, we believe that ED represents a variant of HSIL (CIN 2). Since ED possesses histologic features of both dysplasia and metaplasia, we speculate that it may arise from metaplastic cervical squamous epithelium that has subsequently become infected with intermediate- or high-risk HPV.
American Journal of Surgical Pathology 12/2004; 28(11):1474-84. · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A proportion of cervical squamous intraepithelial lesions encountered in surgical pathology practice contain both metaplastic features and some degree of atypia [so-called eosinophilic dysplasia (ED)] that defy classification according to established criteria. To elucidate the nature of these lesions, we compared 44 cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and 10 squamous metaplasias using a panel of biomarkers and human papillomavirus (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively abundant eosinophilic cytoplasm and distinct cell borders compared with conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic ratio; and 4) focal dysplastic nuclei showing nuclear enlargement, hyperchromasia, variable nuclear membrane irregularities, and appreciable nucleoli. Expression of p16 (p16INK4a), MIB-1 (Ki-67) labeling index, and HPV DNA detection and typing were performed on each case. The majority of EDs showed more than three atypical cells in an entire lesion but lack of apparent features of HSIL. It was common to find neighboring cervical squamous metaplasia and/or conventional SILs (either HSIL or low-grade squamous intraepithelial lesion [LSIL]). Among the 44 cases, 18 (45%) ED lesions were found to be associated with HSIL, 15 (34%) with LSIL or condylomatous lesions, and 13 (30%) EDs were seen without any SILs in the entire specimens. Area of benign squamous metaplasia was found in all ED cases. High levels of p16 and MIB-1 expression were seen in 41 (93%) of 44 ED cases with degrees of immunoreactivity closely resembling those seen with HSIL. Of 16 EDs tested, 13 (81%) were positive for HPV DNAs. Among 10 HPV-positive cases subtyped, 9 (90%) cases contained intermediate- and/or high-risk HPVs and 1 case contained a novel HPV. In the follow-up of pure ED cases, the majority showed presence of dysplastic lesions of either HSIL or LSIL on either loop electric excision procedures or Papanicolaou test samples after a 6- to 10-week period. Therefore, ED represents an unrecognized and potentially clinically significant subgroup of cervical intraepithelial lesions. Based on the unique histologic appearance of ED, its association in some cases with HSIL, the overall immunohistochemical findings, frequent association of ED with intermediate- and/or high-risk HPV infection, and limited follow-up data, we believe that ED represents a variant of HSIL (CIN 2). Since ED possesses histologic features of both dysplasia and metaplasia, we speculate that it may arise from metaplastic cervical squamous epithelium that has subsequently become infected with intermediate- or high-risk HPV.
American Journal of Surgical Pathology 11/2004; 28(11):1474-1484. DOI:10.1097/01.pas.0000141407.10204.c5 · 5.15 Impact Factor