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Science and Technology of Welding & Joining 01/2008; 13(2):118-125. · 1.74 Impact Factor
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ABSTRACT: To identify which patients with locally recurrent cervical carcinoma are potentially curable.
A total of 664 stage IB-IVA patients were examined following surgery or radiotherapy.
Among the 664 patients, 193 (29%) developed recurrence. Sixty-seven (35%) of these recurrences were located in the pelvis alone. Among these 67 recurrences, 24 (35%) were central recurrences and the remaining 43 (65%) were pelvic side-wall recurrences. Of the 24 patients with central recurrences, 8 were salvaged. Of these 8 patients, 3 underwent pelvic exenteration, and 5 received optimal radiotherapy. The recurrent tumor in these 5 survivors who received radiotherapy had consisted of a small (<2 cm) tumor. All 43 patients with pelvic wall recurrence developed progressive disease.
The following patients are potentially curable: patients with a resectable, centrally located tumor who are candidates for pelvic exenteration, and patients with a small central recurrence for whom complete radiation therapy is feasible.
International Journal of Gynecology & Obstetrics 04/2005; 89(1):39-44. · 2.05 Impact Factor
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ABSTRACT: A retrospective analysis was performed to evaluate the prognostic significance of peritoneal cytology in patients with endometrial carcinoma limited to the uterus. A total of 280 patients with surgically staged endometrial carcinoma that was histologically confined to the uterus were examined clinicopathologically. The median length of follow-up was 62 (range, 12-135) months. All patients underwent hysterectomy and salpingo-oophorectomy with selective lymphadenectomy, and only three patients received adjuvant postoperative therapy. No preoperative adjuvant therapy was employed. In all, 48 patients (17%) had positive peritoneal cytology. The 5-year survival rate among patients with positive or negative peritoneal cytology was 91 or 95%, respectively, showing no significant difference (log-rank, P=0.42). The disease-free survival rate at 36 months was 90% among patients with positive cytology, compared with that of 94% among patients with negative cytology, and the difference was not significant (log-rank, P=0.52). Multivariate proportional hazards model revealed only histologic grade to be an independent prognostic factor of survival (P=0.0003, 95% CI 3.02 - 40.27) among the factors analysed (age, peritoneal cytology, and depth of myometrial invasion). Multivariate analysis revealed that histologic grade (P=0.02, 95% CI 1.21-9.92) was also the only independent prognostic factor of disease-free survival. We concluded that the presence of positive peritoneal cytology is not an independent prognostic factor in patients with endometrial carcinoma confined to the uterus, and adjuvant therapy does not appear to be beneficial in these patients.
British Journal of Cancer 02/2003; 88(2):245-50. · 5.04 Impact Factor
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ABSTRACT: We report a rare case of primary synovial sarcoma of the lung. The patient was a 49-year-old woman who presented with a well-defined oval-shaped mass in the left upper lobe on a chest radiograph. A malignant pulmonary tumor was suspected and consequently a left upper lobectomy was performed. Grossly, the tumor measured 5 x 4 cm, was whitish-yellow in color and soft in consistency. Histologically, the tumor showed a dense proliferation of short spindle cells, partly arranged in interlacing fascicles. In some areas a hemangiopericytoma-like pattern, stromal myxoid change and necrosis of various sizes were noted. Numerous mitotic figures were also seen. Immunohistochemically, the tumor cells were positive for epithelial markers such as cytokeratin and epithelial membrane antigen. As these features suggested a monophasic fibrous type of synovial sarcoma, we examined for the presence of SYT-SSXfusion gene transcripts using RNA samples from the frozen tumor tissue. A reverse transcription polymerase chain reaction amplified a single 583-base pair fragment characteristic of synovial sarcoma. As no other tumorous lesions were found during a follow-up period of 1 year, primary synovial sarcoma of the lung was our final diagnosis. This tumor should be considered in the differential diagnosis of round to short spindle cell tumors arising in the lung.
Japanese Journal of Clinical Oncology 06/2001; 31(5):212-6. · 1.78 Impact Factor
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M Tokunou,
T Niki,
K Eguchi,
S Iba,
H Tsuda, T Yamada,
Y Matsuno,
H Kondo,
Y Saitoh,
H Imamura,
S Hirohashi
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ABSTRACT: Hepatocyte growth factor (HGF) plays important roles in tumor development and progression. It is currently thought that the main action of HGF is of a paracrine nature: HGF produced by mesenchymal cells acts on epithelial cells that express its receptor c-MET. In this investigation, we explored the significance of c-MET expression in myofibroblasts, both in culture and in patients with lung adenocarcinoma. We first showed that human myofibroblasts derived from primary lung cancer expressed c-MET mRNA and protein by reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of myofibroblasts was stimulated in a dose-dependent manner by exogenously added recombinant human HGF whereas it was inhibited in a dose-dependent manner by neutralizing antibody to HGF. The addition of HGF in the culture medium stimulated tyrosine phosphorylation of c-MET. The c-MET protein was immunohistochemically detected in myofibroblasts in the invasive area of lung adenocarcinoma. Finally, the prognostic significance of c-MET expression in stromal myofibroblasts was explored in patients with small-sized lung adenocarcinomas. c-MET-positive myofibroblasts were observed in 69 of 131 cases (53%). A significant relationship between myofibroblast c-MET expression and shortened patient survival was observed in a whole cohort of patients including all pathological stages (two-sided P: = 0.0089 by log-rank test) and in patients with stage IA disease (two-sided P: = 0.0019 by log-rank test). These data suggest that the HGF/c-MET system constitutes an autocrine activation loop in cancer-stromal myofibroblasts. This autocrine system may play a role in invasion and metastasis of lung adenocarcinoma.
American Journal Of Pathology 05/2001; 158(4):1451-63. · 4.89 Impact Factor
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ABSTRACT: Vascular endothelial growth factor receptor 3 (VEGFR-3) has been proposed as a marker for lymphatic endothelial cells. This study investigated the expression of VEGFR-3 in the tumour vessels of lung adenocarcinoma and evaluated whether VEGFR-3 staining was useful for identifying lymphatic vessels within the tumour stroma. It also explored whether active growth of lymphatic vessels occurred in lung adenocarcinoma. Formalin-fixed, paraffin-embedded specimens obtained from 60 cases of lung adenocarcinoma, including five cases of pure bronchiolo-alveolar carcinoma (BAC) without stromal, vascular, and pleural invasion, were examined. No VEGFR-3-positive vessels were observed in pure BAC, but varying numbers of VEGFR-3-positive vessels were found in 39 of 55 (70.9%) invasive adenocarcinomas. A comparison of serial sections stained for VEGFR-3, CD31, and laminin-1 showed that most of the VEGFR-3-positive vessels appeared to be blood vessels (CD31-positive, laminin-1-positive), but some had the characteristics of lymphatic vessels (variable staining for CD31, little or no staining for laminin-1). VEGFR-3 staining highlighted lymphatic invasion by cancer cells; this invasion could not be detected by CD31 or haematoxylin and eosin (H&E) staining. Active growth of lymphatic vessels (as indicated by nuclear Ki-67 labelling of the endothelium) was observed in five tumours, four of which showed a high level of lymphatic invasion by cancer cells. It was concluded that VEGFR-3 immunostaining did not discriminate clearly between vascular and lymphatic endothelial cells, since expression of VEGFR-3 can be up-regulated in tumour blood vessels. However, VEGFR-3 staining combined with laminin-1 and CD31 staining would be useful for identifying lymphatic vessels and their invasion by tumour cells in a more objective way. Finally, proliferation of lymphatic endothelial cells may occur in association with lymphatic invasion by cancer cells.
The Journal of Pathology 05/2001; 193(4):450-7. · 6.32 Impact Factor
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ABSTRACT: Laminin-5 plays an important role in cell migration during tissue remodeling and tumor invasion.
The authors studied the expression of laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension < or = 2 cm) using a monoclonal antibody against the laminin gamma2 chain, and they also investigated the associations of laminin-5 with clinicopathologic characteristics. Prognostic significance of increased laminin-5 expression was evaluated using the Kaplan-Meier method and the Cox proportional hazard model.
Overall, laminin-5 expression was observed in 82 cases (80.4%): 7 of 18 (38.9%) bronchioloalveolar carcinomas and 75 of 84 (89.3%) invasive adenocarcinomas. Laminin-5 was preferentially localized in the cytoplasm of tumor cells at the tumor-stromal interface, where budding or dissociation of cancer cells was frequently observed. Overexpression of laminin-5 (24 cases, 23.5%) was associated with vascular invasion (P = 0.021) and stromal fibroblastic reaction (P = 0.005) but not with nodal involvement, lymphatic invasion, or pleural invasion. Survival analysis revealed that overexpression of laminin-5 was associated with shorter patient survival (P = 0.0027 by log rank test). On multivariate analysis, overexpression of laminin-5 was an independent prognostic factor (P = 0.030), as were nodal involvement (P < 0.0001), vascular invasion (P = 0.047), and lymphatic invasion (P = 0.0047) in a whole cohort of patients. Moreover, when patients with Stage I (International Union Against Cancer [UICC] staging system) disease were considered in multivariate analysis, overexpression of laminin-5 was the only significant prognostic factor (P = 0.022), whereas vascular invasion had a marginally significant impact (P = 0.07) on patient survival.
The authors' results showed that laminin-5 is frequently expressed by cancer cells at the invasive front of lung adenocarcinoma. The study concluded that overexpression of laminin-5 may be a useful prognostic factor in patients with small-sized lung adenocarcinoma, especially in Stage I cases.
Cancer 04/2001; 91(6):1129-41. · 4.77 Impact Factor
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ABSTRACT: Vascular endothelial growth factors (VEGFs) C and D are novel members of the VEGF family that show some selectivity toward lymphatic endothelial cells. Recent studies suggest that VEGF-C may be involved in lymphangiogenesis and spread of cancer cells via lymphatic vessels. However, whether other VEGF family members play a role in lymph node metastasis is largely unknown. The aim of the present study was to explore whether expressions of VEGF-A, VEGF-B, VEGF-C, and VEGF-D are correlated with lymph node status in lung adenocarcinoma. Total RNA was isolated from 60 surgical specimens of lung adenocarcinoma with (n = 27) or without (n = 33) lymph node metastasis. The relative mRNA abundance of VEGF-A, VEGF-B, VEGF-C, and VEGF-D was measured by real-time reverse transcription-PCR analysis based on TaqMan fluorescence methodology. We found that, as single factors, expression of none of the four VEGF family members clearly correlated with the presence of lymph node metastasis. The only tendency noted was for higher VEGF-B and VEGF-C and lower VEGF-D levels in the node-positive group. However, two-way scatterplot analysis revealed that tumors with lymph node metastasis were associated with a pattern of low VEGF-D and high VEGF-A, VEGF-B, or VEGF-C, such that the ratios of VEGF-D:VEGF-A, VEGF-D:VEGF-B, or VEGF-D:VEGF-C were significantly lower in the node-positive group. Strikingly, none of the 11 tumors with high VEGF-D levels metastasized to lymph nodes. Furthermore, a low VEGF-D:VEGF-C ratio correlated with the presence of lymphatic invasion, and six of seven tumors with a pattern of very high expression of VEGF-C and low expression of VEGF-D displayed lymph vessel invasion that extended along the bronchovascular tree beyond the main tumor. Finally, levels of VEGF-A, but not VEGF-B or VEGF-C, were higher in tumors with large nodal metastasis (> or = 1 cm) than in those with small (< 1 cm) nodal metastasis. These results support the hypothesis that two VEGF family members are involved in lymph node metastasis at two distinct steps; VEGF-C facilitates entry of cancer cells into the lymph vasculature, whereas VEGF-A promotes the growth of metastatic tumor through angiogenesis. The results also suggest that the balance between VEGF-C and VEGF-D could be important rather than the level of VEGF-C alone. Whether a low VEGF-D level plays a causative role in lymph node metastasis requires further investigation.
Clinical Cancer Research 06/2000; 6(6):2431-9. · 7.74 Impact Factor
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ABSTRACT: The laminin-5 gamma2 chain plays an important role in cell migration during tumor invasion and tissue remodeling.
Laminin-5 gamma2 chain expression in squamous cell carcinomas of the tongue in 67 patients with Stage II, III, or IVA,B (excluding the cases with distant metastasis) was examined immunohistochemically to determine its associations with the clinicopathologic features of each tumor. The predominant staining patterns were categorized as follows: A, few or no tumor cells were positive; B, part of the tumor nest periphery was positive; C, the tumor nest periphery was circumferentially positive; or D, almost all the tumor cells were positive.
Laminin-5 gamma2 chain expression was observed clearly in tumor cell cytoplasm. Of the 67 tumors examined, 6 (9%), 31 (46%), 19 (28%), and 11 (17%) showed staining patterns A, B, C, and D, respectively. With progression from staining pattern A to D, the number of immunopositive tumor cells increased significantly (P<0.0001), and the tumor histology showed significantly more infiltrative growth (P<0.0001) and poorer differentiation (P = 0.0021). Furthermore, both univariate (P = 0.0019) and multivariate (P = 0.0003; hazard ratio = 3.132) analysis of the patients' survival revealed that the prognosis became significantly poorer with progression from staining pattern A to D.
Increased laminin-5 gamma2 chain immunoreactivity, which may reflect a high invasive potential of cancer cells, is a factor indicative of a poor prognosis for patients with squamous cell carcinoma of the tongue.
Cancer 06/1999; 85(11):2315-21. · 4.77 Impact Factor
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ABSTRACT: By clarifying the significance of clinicopathological factors for retroperitoneal lymph node metastasis and survival of patients with endometrial cancer, we suggest ideas for optimal treatment of this disease.
A retrospective study was conducted in 310 women with endometrial cancer who underwent surgery with retroperitoneal lymphadenectomy. To evaluate retroperitoneal lymph node metastasis, age-adjusted and multivariable analyses were carried out for six clinicopathological factors including pathological grade, myometrial invasion, cervical invasion, peritoneal cytology, lymphatic permeation and vascular invasion. To evaluate survival, besides the above factors, a positive rate of metastasis of dissected retroperitoneal lymph nodes was included.
In 40 patients (13%) with nodal metastasis, the average positive rate of metastasis of dissected retroperitoneal lymph nodes was 22%. For retroperitoneal lymph node metastasis, the odds ratio of deep myometrial invasion, cervical invasion and severe lymphatic permeation were 5.97, 2.72 and 12.01, respectively. For survival, the hazard ratios of the positive rates of metastasis of dissected retroperitoneal lymph nodes (both 25% and < 25%), positive peritoneal cytology and poor pathological grade were 7.10, 3.24, 3.82 and 3.27, respectively, and 5-year survival rates for them were 0, 50, 72 and 77%, respectively.
For retroperitoneal lymph node metastasis, lymphatic permeation, deep myometrial invasion and cervical invasion were the independent prognostic factors. For survival, retroperitoneal lymph metastasis, poor pathological grades and positive peritoneal cytology were the independent prognostic factors. The positive rate of metastasis of dissected retroperitoneal lymph metastasis plays an important role in predicting survival of endometrial cancer. Lymph node biopsy is insufficient in treatment of this disease.
Japanese Journal of Clinical Oncology 12/1998; 28(11):673-8. · 1.78 Impact Factor
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ABSTRACT: A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia (AAH) in a 77-year-old woman is reported. Histopathologically, in the resected left upper lobe of the lung, both cancers were diagnosed as well-differentiated papillary adenocarcinoma, and 161 lesions of AAH were also found. Both the cancer lesions and six AAH (greater than 3 mm in diameter) were examined with regard to immunoreactivity of carcinoembryonic antigen (CEA) and p53 gene product, microsatellite instability (MI) and loss of heterozygosity (LOH) on chromosome 9q and 17q by polymerase chain reaction (PCR). Although both cancers expressed CEA, they did not show clonal immunoreactivity for the p53 gene product. Atypical adenomatous hyperplasia expressed CEA weakly and showed no immunoreactivity for p53 gene protein. Both carcinomas showed LOH on chromosome 17q, and one of them showed LOH on chromosome 9q. In six AAH, LOH on chromosome 17q was detected in two tumors, and one of them also showed LOH on chromosome 9q. One AAH, which was negative for LOH on chromosome 17q and 9q, showed MI at D17S791. These results indicated that AAH is a clonal neoplastic lesion with genetic abnormalities and should be called intraepithelial pneumocyte neoplasia, and that each of the numerous papillary lesions in this case was considered to be an independent lesion.
Pathology International 09/1998; 48(8):634-40. · 1.62 Impact Factor
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ABSTRACT: Despite the many studies of genetic alterations in advanced lung carcinomas, few reports have analyzed early stage adenocarcinoma of the lung.
We focused on small pulmonary adenocarcinomas, classified according to recently proposed histological criteria (Noguchi M., et al. Cancer 1995;75:2844-52) which divided adenocarcinomas 2 cm or less in diameter into two groups; one showing replacing growth of the pulmonary alveolar structure [A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with alveolar collapse; C, LBAC with active fibroblastic proliferation] and the other showing non-replacing growth (D, poorly differentiated adenocarcinoma). Ninety-four small pulmonary adenocarcinomas, including 40 of type A and B, 30 of type C and 24 of type D, were examined for loss of heterozygosity (LOH) using microsatellite markers.
The frequencies of LOH were 19.8% in types A and B, 26.8% in type C and 32.7% in type D tumors. There were no significant differences in the frequency of LOH on chromosomes 2p, 3p, 9p and 17q among tumor types. However, on 17p, the frequency of LOH was significantly lower for types A and B than for type C or D. Three out of six type C tumors which were positive for LOH at several loci showed different LOH patterns in two areas (central and peripheral regions).
Allelic losses were detected in very early adenocarcinomas and the frequency of LOHs on chromosome 17p increased during malignant progression of the tumor. Heterogeneous genetic alterations were demonstrated even in small pulmonary adenocarcinomas.
Japanese Journal of Clinical Oncology 05/1998; 28(4):240-4. · 1.78 Impact Factor
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ABSTRACT: Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle alpha-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.
The Journal of Cell Biology 03/1998; 140(6):1383-93. · 10.26 Impact Factor
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ABSTRACT: We report on eight patients who developed brain metastases following uterine cervical cancer. The mean interval between diagnosis of the primary cancer and diagnosis of the brain metastasis was 28.4 months (range: 6.1-61.8 months). Nausea and vomiting due to increased intracranial pressure were the most frequent symptoms. Surgical excision of the brain lesions, followed by postoperative radiotherapy, was performed in three patients. The other five patients received only cranial radiotherapy. When the metastatic brain lesions were detected, other distant metastatic lesions were confirmed at the same time in five patients. The median survival time after diagnosis of the brain metastases was only 3.0 months.
Japanese Journal of Clinical Oncology 02/1998; 28(1):27-9. · 1.78 Impact Factor
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ABSTRACT: To improve cancer chemotherapy, a better understanding of the molecular mechanisms of drug resistance is essential. To identify the molecules responsible for drug resistance that is unrelated to MDR1 or MRP gene products, a eukaryotic expression cDNA library of cis-diamminedichloroplatinum(II) (CDDP)-resistant ovarian cancer TYKnuR cells was introduced into Cos-7 cells. After repeated CDDP selection, cDNA homologous to murine semaphorin E was isolated from surviving cells. Human semaphorin E (H-sema E) was overexpressed in CDDP-resistant cell lines and was readily induced not only by diverse chemotherapeutic drugs but also by x-ray and UV irradiation. Transfection of H-sema E conferred a drug-resistant phenotype to CDDP-sensitive cells. In addition, the aberrant expression of H-sema E protein was detected immunohistochemically in 14 of 42 (33.3%) recurrent squamous cell carcinomas removed at autopsy after extensive radiochemotherapy. Recently, another member of the semaphorin family, CD100, was shown to significantly improve the viability of B lymphocytes. These results suggest the involvement of semaphorins in diverse cell survival mechanisms.
Proceedings of the National Academy of Sciences 01/1998; 94(26):14713-8. · 9.68 Impact Factor
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ABSTRACT: Through yet unidentified mechanisms, squamous epithelial cells become committed to terminal differentiation after detachment from the basement membrane. In squamous cell carcinoma, these mechanisms seem to be disturbed. A murine monoclonal antibody, designated NCC-Lu-226 (IgG1, K), which recognizes an antigen expressed in basal cells of squamous epithelium at the epithelio-connective tissue border, was obtained. A cDNA clone encoding the antigen was isolated from a cDNA library by immunoselection. DNA sequencing and a database search revealed that this cDNA clone was identical to a hemidesmosomal transmembrane protein, bullous pemphigoid antigen 2 (BPA-2; also known as BPAG2, BP180, or type XVII collagen). Immunoelectron microscopy validated the specific reactivity of this monoclonal antibody with skin hemidesmosomes. Enhanced expression and abnormal distribution of BPA-2 was revealed immunohistochemically in various precancerous and cancerous tissues, including solar keratosis (4 of 5), Bowen's disease (3 of 5), invasive squamous cell carcinoma (7 of 7) of the skin, and squamous cell carcinoma of the lung (14 of 14), esophagus (12 of 13), and cervix (14 of 17). The specific expression of BPA-2 protein in squamous cell carcinoma was confirmed by RT-PCR and Northern hybridization. BPA-2 has possible phosphorylation sites and is actually phosphorylated in cultured keratinocytes and squamous cell carcinoma. The aberrant expression of BPA-2 may reflect dysfunction of the hemidesmosome that occurs as a relatively early event in multistep carcinogenesis of squamous epithelium.
Laboratory Investigation 11/1996; 75(4):589-600. · 3.64 Impact Factor
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ABSTRACT: In order to evaluate the alterations of nuclear p53 accumulation in early stage adenocarcinomas of the lung, nuclear p53 accumulation by small-sized peripheral adenocarcinomas of the lung was examined immunohistochemically. Peripheral adenocarcinomas of the lung, 2 cm or less in diameter, have been classified into two groups; one showing replacing growth of the pulmonary alveolar structure and the other showing non-replacing growth. The former group has been subdivided into three microscopic subtypes: type A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with foci of pulmonary alveolar structural collapse; and C, LBAC with foci of active fibroblastic proliferation. Type C is thought to be advanced carcinoma, which develops progressively from types A and B. Two of 32 (6%) types A and B carcinomas, 37 of 133 (28%) type C carcinomas and 14 of 35 (40%) non-replacement-type adenocarcinomas showed positive nuclear staining for p53. The positive staining frequency was significantly higher for type C than for types A and B (P < 0.05). These results suggest that nuclear p53 accumulation occurs in the transition from the early to advanced stages of replacement-type adenocarcinoma development and it may be a clinically useful indicator of the degree of tumor malignancy.
Pathology International 08/1996; 46(7):486-90. · 1.62 Impact Factor
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ABSTRACT: Adenocarcinoma of the uterine cervix (CxAd) is one of the most distressing malignancies of the female reproductive system because of its tendency to spread aggressively and to be resistant to radiation and systemic therapies. To clarify the prognostic significance of p53 alteration in CxAd, we immunohistochemically examined the incidence of p53 nuclear accumulation, which is considered to be mostly parallel with p53 gene mutation, and its association with clinicopathological parameters in 26 patients with CxAd. The overall incidence of p53 nuclear accumulation was 46% (12 of 26), being higher in groups with clinically advanced disease, higher degrees of cellular atypia, and deeper myometrial invasion, but significantly lower in patients with integration of human papillomavirus (HPV) type 16 or 18 DNA. Nuclear p53 immunoreactivity as well as lymph node status, depth of invasion and the absence of HPV-DNA integration were significant indicators of a poor prognosis. Examination of p53 nuclear accumulation could be applied to biopsy material, and would be of practical assistance in predicting the prognosis of CxAd both preoperatively and postoperatively.
Japanese journal of cancer research: Gann 12/1995; 86(11):1049-53.
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ABSTRACT: The frequency of c-Ki-ras mutation was examined by polymerase chain reaction (single-strand conformation polymorphism and direct sequencing analysis) and its association with histological parameters was analyzed in 110 endometrial adenocarcinoma hysterectomy specimens. The c-Ki-ras mutation was detected in 24 cases (22%). It occurred irrespective of tumor size, stage or histological grade, and was more frequent in tumors associated with endometrial hyperplasia (11 of 20, 55%) than in those without (10 of 73, 14%). In addition, the frequency of the mutation was significantly higher in tumors showing an infiltrative growth pattern accompanied by a stromal response consisting of edematous fibrous tissue (19 of 58, 33%), than in those which revealed an expansive growth pattern without such a stromal reaction (five of 52, 10%). Even among tumors showing the infiltrative growth pattern, the frequency of c-Ki-ras mutation was especially high (48%) in grade I cases in comparison with grade II or III cases (20% and 19%). Mutational activation of the c-Ki-ras gene may act at two points in the developmental pathway of endometrial adenocarcinoma by enhancing evolution of hyperplasia to adenocarcinoma, and by producing an infiltrative growth with a fibrosing stromal response.
International Journal of Gynecological Pathology 08/1995; 14(3):255-9. · 1.45 Impact Factor
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ABSTRACT: Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma.
Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns.
Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types.
Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis.
Cancer 07/1995; 75(12):2844-52. · 4.77 Impact Factor
