-
[show abstract]
[hide abstract]
ABSTRACT: This study aimed to assess the risk of progression/persistence of squamous intraepithelial lesions (SILs) during pregnancy according to the age of the woman, the grade of the lesion, the type of human papillomavirus (HPV) infection, and the mode of delivery.
Eighty pregnant women with abnormal cytologic result at the first antenatal visit were evaluated. Postpartum cytologic and histologic findings were compared with the antepartum findings.
There were 40 patients with low-grade SIL and 40 with high-grade SIL (HSIL). The overall regression rate was 32.5%. There were 19 patients 25 years or younger and 61 patients older than 25 years. The regression rate among younger patients was 52.6% versus 26.2% among those older than 25 years (relative risk [RR] = 2.01, 95% confidence interval [CI] = 1.10-3.66). The regression rate was 45% in the group of low-grade SIL and 20% in the group of HSIL (RR = 2.25, 95% CI = 1.11-4.57). In patients with HSIL, those older than 25 years had a 2-fold increased risk of progression/persistence than younger patients. High-risk HPV-positive samples were typed in 44 cases, 21 of which (47.7%) were positive for HPV-16. The regression rate was 9.5% for HPV-16-positive cases and 52.2% for HPV-16-negative cases (RR = 5.48, 95% CI = 1.39-21.68). The risk of progression or persistence of the lesion according to mode of delivery did not show significant differences (RR = 1.15, 95% CI = 0.82-1.63).
Age of the patient older than 25 years, HSILs, and HPV type 16 infection are risk factors for the progression or persistence of intraepithelial lesions of the cervix in the postpartum period.
Journal of Lower Genital Tract Disease 11/2011; 16(1):34-8. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous work from our laboratory has demonstrated that the expression of the ribosomal protein Rplp1 immortalizes primary cells and is involved in transformation. To investigate the role of the P proteins in tumorigenesis, we examined the messenger RNA expression levels of Rplp0, Rplp1, and Rplp2 in a series of 32 patients with gynecologic tumors. The messenger RNA expression level of all 3 P proteins was increased significantly in the tumor tissue, compared with normal tissue. In addition, a total of 140 biopsies of gynecologic cancers (46 endometrioid and 94 ovarian) were investigated. An up-regulation of P protein expression was observed by immunohistochemistry in an average of 27% of the tumors, as compared with normal tissues. Moreover, the level of P protein up-regulation correlated significantly with p53 expression in serous ovarian cancers. This is an important fact because the level of overexpression of the P proteins correlated with the presence of lymph node metastases in serous ovarian cancers. We also observed that endometrial carcinomas that had invaded the myometrium overexpressed P proteins in the invasive front. In addition, we found that the P proteins are up-regulated in a considerable number of patients with the most common types of cancer. Overall, our study shows that P proteins are involved in human cancer and indicates that the expression level of these proteins could be useful as a prognostic marker in specific subtypes of gynecologic tumors.
Human pathology 10/2010; 42(2):194-203. · 3.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The association between cervical cancer and uterine prolapse is rare and sparsely represented in literature, despite the high incidence of the latter. The suitable treatment in this clinical situation is not defined. The objective of this article is to review published cases about this clinical condition.
We report a case of cervical cancer in prolapsed uterus treated with radical hysterectomy performed totally by laparoscopic approach, and review other case reports published about this clinical condition.
We present the first case reported in literature in our knowledge of cervical cancer in prolapsed uterus treated with radical hysterectomy performed totally by laparoscopic approach. Treatments previously reported are vaginal hysterectomies with adjuvant radiotherapy or concomitant chemo-radiotherapy.
Radical hysterectomy can be correctly performed totally by laparoscopic approach even when cervical cancer is associated with severe uterine prolapse.
Archives of Gynecology 07/2010; 282(1):63-7. · 0.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma.
Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months.
Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated.
In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.
International journal of radiation oncology, biology, physics 05/2009; 75(5):1316-22. · 4.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hus1 and Rad9 are proteins involved in DNA damage checkpoint regulation, which is required for the maintenance of genomic stability. In addition to checkpoint activation, mammalian cells also use apoptosis to eliminate cells with severe DNA damage. Interestingly, Rad9 was shown to be directly involved in apoptosis as well. Despite the knowledge of molecular mechanisms on how Hus1 and Rad9 act in response to DNA damage, little is known about the role of these 2 proteins in cancer progression. In this study, we analyzed the expression of Rad9 and Hus1 in epithelial ovarian tumors and correlated them to clinopathological parameters and apoptotic biomarkers (p53, Bcl-2, and Bax). Histological sections from 114 primary ovarian epithelial tumors were stained with antibodies using the streptavidin-biotin method. In addition, mitotic and apoptotic indices (both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling assay) were also measured. We found that Rad9 expression correlated closely to significance only with the apoptotic and mitotic indices (P = 0.056 and 0.059, respectively). Hus1 levels correlated significantly with the clinicopathologic factors of bad prognosis, including FIGO (International Federation of Gynecology and Obstetrics) stage (P < 0.002) and with the p53 expression (P < 0.001), Bax expression (P < 0.008), mitotic index (P < 0.001), and apoptotic index (P < 0.003).
International Journal of Gynecological Pathology 02/2008; 27(1):24-32. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective was to establish the importance of apoptosis-related genes and the apoptotic index (AI) as prognostic factors in patients with epithelial ovarian tumours.
Tumour specimens from 130 epithelial ovarian tumours were examined for expression of p53, bcl-2 and bax proteins. The apoptotic index was evaluated by modified terminal deoxynucleotide-transferase-mediated digoxigenin triphosphate-biotin nick end-labelling (TUNEL) methods and by haematoxylin-eosin (H-E) staining. Other clinical and histopathological variables were also analysed. Statistical analyses were performed using the SPSS 10.0 package.
The apoptotic index detected by H-E and enzymatic assay was high in the majority of carcinomas (serous, endometrioid and clear cell (p=0.001). In the univariate survival analysis, high apoptotic index, high p53 and low bcl-2 expression, significantly correlated with shorter survival and shorter disease-free periods (p<0.01). In multivariate analysis the age (p=0.026; CI: 1.035-1.066 and p=0.011; CI: 1.835-2.077), FIGO stage (p=0.017; CI: 1.385-4.514 and p=0.024; CI: 1.217-1.940), p53 expression (p=0.03; CI: 1.017-1.627 and p=0.02; CI: 1.050-2.350) and apoptotic index (p=0.019; CI: 1.375-1.750 and p=0.019; CI: 1.442-2.085) were revealed to be independent prognostic factors for survival and recurrence, respectively.
Our results indicate that the apoptotic index and p53 nuclear accumulation are independent predictive factors of recurrence and short survival. Our data also suggest different patterns of alterations for the various tumour types.
European Journal of Obstetrics & Gynecology and Reproductive Biology 01/2007; 130(1):121-8. · 1.97 Impact Factor
-
Jesús Planagumà,
Marta Gonzalez,
Andreas Doll,
Marta Monge,
Antonio Gil-Moreno,
Teresa Baró, Angel García,
Jordi Xercavins,
Francesc Alameda,
Miguel Abal,
Jaume Reventós
[show abstract]
[hide abstract]
ABSTRACT: We have recently described RUNX1/AML1 up-regulation in endometrioid endometrial carcinoma (EEC), proposing that it could play a role during the initial steps of myometrial infiltration. Some cell cycle regulators, including the cyclin-dependent kinase inhibitor p21WAF1/CIP1, have been described as targets of RUNX1/AML1. In this study, we have attempted to address the question of whether RUNX1/AML1, acting both as a gene transcription activator and a repressor, depending on the context, can be correlated with the expression of p21WAF1/CIP1 in gynecologic malignancies, in particular in EEC, where the role of p21(WAF1/CIP1) remains controversial. Toward this end, we analyzed p21WAF1/CIP1 expression in a large panel of EEC samples using real-time quantitative polymerase chain reaction and tissue microarray immunohistochemistry, and evaluated the extent to which RUNX1/AML1 and p21WAF1/CIP1 interacted in the EEC samples. The strong correlation found between RUNX1/AML1 and p21WAF1/CIP1 suggested cooperation between the 2 genes in EEC, especially in those tumor samples corresponding to stage IC carcinomas, infiltrating more than 50% of the myometrium. We hypothesize that p21WAF1/CIP1 and RUNX1/AML1 interact during the initial steps of tumor dissemination in EEC, and we discuss mechanisms that could underlie myometrial infiltration and/or the promotion of an invasive phenotype.
Human Pathlogy 09/2006; 37(8):1050-7. · 2.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To elucidate alterations in gene expression in endometrioid endometrial carcinoma (EEC), differential gene expression profiling was previously described in both tumour and non-tumour contexts, and the up-regulation of the RUNX1/AML1 proto-oncogene in EEC was characterized. Among the set of genes found to be up-regulated significantly in EEC, the most relevant, ERM/ETV5, corresponds to the PEA3 subfamily and is a member of the Ets family of transcription factors that contain the Ets DNA-binding domain and are involved in matrix remodelling. In the present work, an attempt was made to characterize the expression of ERM/ETV5 in EEC throughout the process of tumourigenesis. Gene expression levels of ERM/ETV5 were quantified by real-time quantitative PCR (RT-Q-PCR) using a large panel of samples ranging from non-invasive IA to metastatic IIIA stages, and protein expression was characterized by tissue array immunohistochemistry (TMA). RT-Q-PCR validated ERM/ETV5 up-regulation in EEC and demonstrated a specific and significant increase restricted to those tumour stages associated with myometrial invasion. TMA showed that ERM/ETV5 up-regulation correlated mainly with the transition from atrophic endometrium to hyperplasia and carcinoma during tumour progression. Furthermore, ERM/ETV5 gene and protein expression levels were associated with low tumour grade. Finally, ERM/ETV5 up-regulation correlated with that of RUNX1/AML1. All of these results lead to the proposal of a co-operative role between ERM/ETV5 and RUNX1/AML1 during the early events of endometrial tumourigenesis, which may be associated with a switch to myometrial infiltration.
The Journal of Pathology 01/2006; 207(4):422-9. · 6.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Struma ovarii are quite unusual lesions that represent less than 3% of all teratomas and its malignant transformation is very uncommon. The clinical manifestations are characteristic of pelvic tumor and the hormonal metabolism is not usually modified. Radiography, employing ultrasound procedures, is the most commonly used pre-surgical detection method but only histological examination makes the diagnosis. The malignance recognition by pathological study not always is easy; in this sense, it requires an exhaustive sampling of the lesion, being specially carefully in some aspects related with malignant transformation such as extending beyond the capsula and involving peripheral tissues. A thyroidal differentiation must be confirmed by immunohistochemical study and other local processes with similar histology should be ruled out. Given the exceptional character of malignant forms, there does not appear to be unanimous agreement on a standard therapy with a somewhat uncertain prognosis.
We show a case of a 22-year-old patient with an ovarian tumor that was discovered by ultrasound examination and surgically removed. The histologic study revealed struma ovarii with malignant transformation towards follicular carcinoma and unlike previously published cases, had a prevalence of clear cells. The patient was submitted to a second surgical staging intervention, with conservative surgery and follow-up controls being considered given that was a young woman with a desire to have children. Laparoscopy was employed as the best method capable to facilitate shorter convalescence.
Clinical and analytical controls, measuring thyroglobulin levels, has been satisfactory up to the present.
Archives of Gynecology and Obstetrics 04/2005; 271(3):251-5. · 1.28 Impact Factor
-
Jesús Planagumà,
María Díaz-Fuertes,
Antonio Gil-Moreno,
Miguel Abal,
Marta Monge, Angel García,
Teresa Baró,
Timothy M Thomson,
Jordi Xercavins,
Francesc Alameda,
Jaume Reventós
[show abstract]
[hide abstract]
ABSTRACT: Endometrial carcinoma is the most common gynecological malignant disease in industrialized countries. Two clinicopathological types of endometrial carcinoma have been described, based on estrogen relation and grade: endometrioid carcinoma (EEC) and non-EEC (NEEC). Some of the molecular events that occur during the development of endometrial carcinoma have been characterized, showing a dualistic genetic model for EEC and NEEC. However, the molecular bases for endometrial tumorigenesis are not clearly elucidated. In the present work, we attempted to identify new genes that could trigger cell transformation in EEC. We analyzed the differential gene expression profile between tumoral and nontumoral endometrial specimens with cDNA array hybridization. Among the 53 genes for which expression was found to be altered in EEC, the acute myeloid leukemia proto-oncogene, RUNX1/AML1, was one of the most highly up-regulated. The gene expression levels of RUNX1/AML1 were quantified by real-time quantitative PCR, and protein levels were characterized by tissue array immunohistochemistry. Real-time quantitative PCR validated RUNX1/AML1 up-regulation in EEC and demonstrated a specific and significantly stronger up-regulation in those tumor stages associated with myometrial invasion. Furthermore, tissue array immunohistochemistry showed that RUNX1/AML1 up-regulation correlates to the process of tumorigenesis, from normal atrophic endometrium to simple and complex hyperplasia and then, on to carcinoma. These results demonstrate for the first time the up-regulation of RUNX1/AML1 in EEC correlating with the initial steps of myometrial infiltration.
Cancer Research 01/2005; 64(24):8846-53. · 7.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Two distinct types of vulvar squamous cell carcinomas and their precursors, vulvar intraepithelial neoplasias (VIN), which differ in terms of clinical presentation and behavior, have been delineated. Human papillomavirus (HPV)-associated carcinomas are of basaloid or warty type, whereas tumors unrelated to HPV are usually keratinizing and differentiated. Thus, the major stratifying factor for vulvar carcinomas and VIN is their etiopathogenetic relationship with HPV. However, because of technical difficulties in confidently detecting HPV in tissues, this diagnosis is usually based on purely morphologic criteria, even though some overlap exists between these histologic types. Recently, the tumor suppressor protein p16 has been shown to be specifically overexpressed in HPV-related carcinomas and premalignant lesions of the uterine cervix, oral cavity, and anus, but the presence of p16 vulvar squamous lesions has not been examined. We have evaluated the immunohistochemical expression of p16 in a series of formalin-fixed, paraffin-embedded vulvar carcinomas and their putative precursors. p16 was strongly positive in all cases of basaloid/condylomatous VIN3 (30/30) and basaloid (7/7) and warty (3/3) carcinomas. In contrast, p16 was almost consistently negative in normal skin, squamous cell hyperplasia (0/20), lichen sclerosus (0/19), differentiated (simplex) VIN3 (0/11), verrucous carcinoma (0/2), and keratinizing squamous cell carcinoma (3/33, 9%). One of the keratinizing squamous cell carcinomas positive for p16 occurred in a 25-year-old woman and the other two were associated with small foci of basaloid VIN3 adjacent to the tumor, suggesting a probable relationship with HPV. p16 was positive in 6 of 10 of basal cell carcinomas. In conclusion, p16 immunostaining is a good discriminator between HPV-associated and HPV-unrelated vulvar carcinomas and VIN, although it cannot differentiate basaloid squamous and basal cell carcinoma.
International Journal of Gynecological Pathology 08/2004; 23(3):206-14. · 1.45 Impact Factor
