Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions.

We immunohistochemically analyzed kallikrein 4 protein (hK4) expression in patients with epithelial ovarian carcinoma (181 malignant effusions and 103 solid carcinoma lesions). Expression of hK4 was also studied in 32 effusions using immunoblotting. Carcinoma cells expressed hK4 in 144 (79.6%) of 181 effusions and 85 (82.5%) of 103 solid tumors. Expression was seen in 51% or more of tumor cells in 70 effusions but often was limited to 5% or fewer cells in solid tumors (P = .009, primary tumors vs effusions; P = .002, metastases vs effusions). Immunoblotting showed hK4 expression in 31 of 32 specimens. Stromal cell hK4 expression, seen in 48 (46.6%) of 103 lesions, was significantly higher in primary tumors than metastases (26/43 vs 22/60, P = .019). hK4 expression in tumor cells was significantly lower in International Federation of Gynecology and Obstetrics stage IV than stage III tumors (P = .004, all lesions; P = .012, primary tumors). hK4 expression in carcinoma cells was associated with longer overall survival (not significant; P = .14, peritoneal effusions). hK4 is expressed widely in ovarian carcinoma; levels in carcinoma cells are highest in effusions, which might be related to loss of stromal contribution and/or altered microenvironment. hK4 expression in carcinoma cells of effusions or solid tumors does not predict survival.

Short stricture of the rectum regressing on discontinuation of hormone replacement therapy: endoscopic appearance, multiple biopsies and clinical improvement insufficient for diagnosis.

A short, benign-looking stricture of the rectum presented itself clinically as subileus in a middle-aged woman after 5 years on hormone replacement therapy (HRT) and 8 years after curative surgery for cancer of the ovaries. Radiological work-up and multiple, repeated biopsies supported the endoscopically appearing benign nature of the lesion, and the stricture subsided after discontinuation of HRT. Re-introduction of HRT again caused subileus. At surgery, there was no suspicion of malignant disease. Histological examination of the resection specimen did, however, show metastasis from the ovarian cancer.

Cytogenetic characterization of tumors of the vulva and vagina.

Neoplasms of the vulva and vagina account for less than 5% of all female genital tract cancers. Squamous cell carcinoma (SCC) represents more than 70% of the cases in both locales, followed by melanoma, basal cell carcinoma, Paget's disease, and other carcinoma subtypes. Until recently, only few cases had been analyzed by chromosome banding techniques and karyotyped, and also the number subjected to molecular cytogenetic analysis remains low. To understand better the genetic changes harbored by the neoplastic cells in cancer of the vulva and vagina, we analyzed cytogenetically 51 such tumors, finding karyotypic abnormalities in 37. All tumors were analyzed by G-banding, sometimes supplemented by multicolor fluorescence in situ hybridization, and a subset of tumors was also analyzed by comparative genomic hybridization. The two cytogenetically abnormal cases of Paget's disease both had two clones, one with gain of chromosome 7 as the sole change, the other with loss of the X chromosome among, in one case, other aberrations. The four cytogenetically abnormal malignant melanomas (three of the vulva, one of the vagina) presented complex karyotypes with aberrations involving different chromosomes but most often chromosome 1, specifically 1p12-q41. In the 31 cytogenetically abnormal SCCs, different clonal karyotypic abnormalities were seen. Intratumor heterogeneity with multiple clones was observed in 11 cases. The clones were cytogenetically unrelated in eight tumors but related in three, indicating that in the latter clonal evolution had taken place from a single malignantly transformed cell. The main chromosomal imbalances were gains of, or from, chromosome arms 3q, 5p, 8q, 9q, and 19q, and loss from 11q. Breakpoint clusters were seen in 11q13-23, 2q22-35, and 19q13, as well as in the centromeres and pericentromeric bands of chromosomes 3, 8, 9, 13, 14, and 22.

p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas.

OBJECTIVE: Aberrant expression of the cell cycle kinase inhibitors p16, p21, and p27 has been associated with poor prognosis in a variety of human malignancies. Little is known, however, about their clinical impact in vulvar carcinoma patients. Thus, we analyzed a larger series of vulvar squamous cell carcinomas and compared the results with clinical outcome. METHODS: A total of 224 vulvar squamous cell carcinomas were immunohistochemically investigated for expression of p16, p21, and p27 using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system. RESULTS: High p16 (> or =5%) positive nuclear immunostaining was found in 69 (31%) cases, high p21 (any staining) protein levels was detected in 95 (42%) cases, and low p27 (< or =50% positive nuclei) staining was seen in 170 (76%) cases. High expression of p16 was related to lower patient age and low expression of p53. High expression of p16 indicated a better prognosis in the multivariate analysis (RR = 0.5, 95% CI = 0.2-1.0) and less risk of developing lymph node metastasis (OR = 0.3, 95% CI = 0.2-0.7). High level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR = 3.4, 95% CI = 1.3-9.3). We found no significant correlation between the expression of p27 and any of the clinicopathological variables. CONCLUSIONS: Our study indicates a prognostic relevance for p16 and p21 immunoreactivity. Low level of p16 protein and high level of p21 protein were associated with a shorter disease-related survival. We did not find p27 protein expression to be useful as a prognostic indicator in vulvar carcinoma patients.