The aim of this study was to detect activated c-K-ras by gene point mutation and to find c-erbB-2 gene amplification with p185 expression in association with the c-K-ras gene product p21 in the human endometrium. Specimens obtained from 25 normal, 31 hyperplastic and 72 malignant samples of the human endometrium were examined for point mutation in codons 12, 13 and 61 of the c-K-ras by direct sequencing and c-erbB-2 gene amplification with p185 and p21 expression by differential polymerase chain reaction (DPCR) and immunohistochemistry. Neither the normal endometrium nor endometrial hyperplasias were found to have mutations in the c-K-ras gene, although a double mutation of codons 12 and 13 as a single-point mutation was observed in one case of endometrioid carcinoma (2.8%). In each of two other cases of endometrioid carcinoma (2/72), two single-point mutations of codon 13 (5.6%) were shown. Using DPCR, we found c-erbB-2 to be amplified in 15 premalignant (48%) and 45 malignant (63%) samples. We noticed that nonamplification of the c-erbB-2 gene was associated with the absence of immunoreactivity. Our data indicate that, while c-erbB-2 plays a role in the early development of endometrioid carcinomas, c-K-ras gene activation by point mutation does not.

Biomarkers, Tumor↗

PubMedDate not supplied

Humoral p53 antibody response is a prognostic parameter in ovarian cancer.

BACKGROUND: Mutant p53 protein may become the target of a tumor-specific humoral and cellular immune response. MATERIAL AND METHODS: We used a specific qualitative p53 antibody ELISA to investigate serum samples of 33 patients with ovarian cancer taken prior to therapy. Additionally, we sought to evaluate whether p53 antibodies are also present in the sera of 17 patients with benign ovarian tumors. RESULTS: p53 antibodies were detected in 36% of serum samples. There was a statistically significant association between p53 serum antibody response and poor overall survival (p < 0.006). No significant associations were found between p53 antibody status and histological type, histological grade, and tumor stage. In 81% of serum samples, no changes from p53 antibody negativity to positivity or vice versa during follow-up were observed. p53 antibodies were also detected in the sera of 18% of patients with benign ovarian tumors. CONCLUSIONS: The results of this preliminary study suggest that a p53 antibody response in patients with ovarian cancer is associated with poor prognosis. A qualitative method of p53 antibody detection cannot be used to monitor the clinical course of ovarian cancer.

Antibodies, Neoplasm↗

PubMedDate not supplied

Papilloma virus and c-erbB-2 expression in diseases of the mammary nipple.

PURPOSE: The detection of low/intermediate/high risk genital groups of human papillomavirus (HPV) in correlation with a growth-factor receptor c-erbB-2 in benign tumors of the mammary nipple. MATERIALS AND METHODS: Ten nipple duct adenomas (NDAs) and twenty papillomas, all embedded in paraffin and taken from the breast, were analyzed for HPV DNA of the low- and high/intermediate-risk groups. Polymerase chain reaction (PCR) with HPV consensus primers (types 6/11/16/18/33) and dot-blot hybridization with type-specific primers were used for the detection of these HPV-DNA sequences. Indirect in situ PCR (ISPCR) was also used in one case of an HPV-DNA-positive papilloma. In addition, we examined c-erbB-2 oncogene expression in NDAs and central carcinomas of the mamma from an immunohistochemical perspective. RESULTS: Using PCR and dot-blot hybridization we could not detect the gene sequences that are specific for the low- and high/intermediate-risk groups in any of the ten NDAs. Regarding the 20 cases of papilloma, a positive result for HPV types 6/11 was detected by indirect ISPCR; in one case in combination with a condyloma of the skin around the mammary nipple. The oncogene expression of c-erbB-2 displayed a strong signal in the papilloma cells and in the NDAs of the breast. CONCLUSION: Our results showed that the HPV-DNA types of the low- and high/intermediate-risk groups are without relevance for the pathogenesis of benign diseases of the nipple. It was, therefore, not possible to establish a correlation between the oncogene expression of c-erbB-2 and the HPV-DNA types.

Adenoma↗

PubMedDate not supplied

Fertility after operations of extrauterine pregnancy.

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Abortion, Spontaneous↗

PubMedDate not supplied

pS2 and PAI-1 in ovarian cancer: correlation to pathohistological parameters.

The estrogen regulated pS2 protein and the Plasminogen Activator Inhibitor type 1 (PAI-1) have been reported as important tumor parameters both in breast and in ovarian cancer. We analysed the cytosolic concentrations of pS2 in 111 ovarian carcinoma and the cytosolic concentrations of PAI-1 in 104 ovarian cancers by RIA and ELISA. Using a cut-off level of 2 ng/mg protein we found 27% pS2+ tumors. We observed 42% PAI-1+ tumors using a out-off level of 1 ng/mg. We found a statistically significant decline in the pS2 status corresponding with an increase in the PAI-1 status from well to poor differentiation grade. The highest levels of pS2 and the lowest levels of PAI-1 were measured in borderline carcinoma. Significantly higher concentrations of pS2 were measured in mucinous over serous carcinoma. We found no significant correlation between PAI-1 and histologic subtypes, or between pS2 or PAI-1 and estrogen receptor status, progesterone receptor status, age and tumor stage. To conclude, we found pS2 and PAI-1 concentrations to be correlated with the grade of differentiation. A correlation between protein status and histologic subtypes could be observed for pS2 but not for PAI-1.

Adolescent↗

PubMedDate not supplied

Prostate specific antigen (PSA) in breast and ovarian cancer.

Prostatic specific antigen (PSA) is commonly used for the diagnosis and monitoring of prostatic adenocarcinoma, and has recently been detected in breast cancer and it is also thought to be produced by ovarian cancer. To examine the prognostic value of PSA tumor expression, we investigated the tumor cytosols of 26 patients with breast cancer and of 16 women with ovarian cancer. We used a chemiluminescence immunoassay for the quantitative determination of PSA (detection limit 0.003 ng/ml). The median PSA level in breast cancer patients was 0.31 ng/mg (minimum 0.003, maximum 4.4). PSA expression was significantly lower in poorly differentiated breast cancers compared to moderately and highly differentiated tumors. Advanced lymph node metastases were also correlated with lower PSA expression. We found no correlation with relapse free or overall survival. Median PSA level in our ovarian cancer patient collective was 0.014 ng/mg (minimum 0.003, maximum 0.046). We found a significant correlation between PSA expression and the estrogen receptor content of the tumor. PSA expression showed no correlation with histological grading, tumor size or other tumor characteristics in ovarian cancer. There was no correlation with relapse free or overall survival in ovarian cancer patients. Our study demonstrates that PSA is expressed in ovarian malignancies but at a lower level compared to breast cancer tissue. PSA was not able to identify a subset of patients with good prognosis in breast and in ovarian cancer patients.

Adenocarcinoma↗