M. Teresiak

PURPOSE: Germline mutations of the BRCA2 gene are involved in the development of a considerable number of male breast cancer cases. Although phenotypic differences have been observed between sporadic and BRCA-related breast carcinomas, conflicting data exist on the differences in prognosis of women with hereditary and sporadic breast cancer. The purpose of the study was to investigate the prognostic value of BRCA2 status in male breast carcinoma (MBC). EXPERIMENTAL DESIGN: We studied 43 male breast cancer patients, including 12 with BRCA2 mutations. Tumor samples were characterized immunohistochemically using antibodies to estrogen receptor, progesterone receptor, and androgen receptor (AR). RESULTS: BRCA2-related tumors presented at the earlier age compared with sporadic tumors (P = 0.005). Patients positive and negative for BRCA2 mutations did not differ with respect to tumor size, lymph node involvement, histological grade, and sex hormone receptor status. Five-year disease-free survival (DFS) and overall survival (OS) were significantly decreased in BRCA2-positive patients (67% versus 28% for BRCA2-negative versus positive patients, respectively, P = 0.017 for DFS; 86% versus 25%, P = 0.006 for OS). Shorter survival was also correlated with expression of AR in tumor tissue (74% versus 33% for patients with tumors staining negatively and positively for AR, P = 0.029 for DFS; 71% versus 57%, P = 0.05 for OS). CONCLUSIONS: The BRCA2 mutations and AR expression in tumor tissue are independent adverse factors for MBC prognosis. BRCA2-related MBC presents at the earlier age compared with non-BRCA2-related cancer, but do not differ with respect to other clinicopathological features.

Breast cancer is a rare disease in men. Germ-line mutations in BRCA2 and androgen receptor (AR) genes are thought to be responsible for a proportion of male breast cancer cases. The present study was performed on a series of 37 consenting patients not selected for family history of breast/ovarian cancer. The entire coding region of the BRCA2 gene and two exons of the AR gene were analyzed for germ-line mutations to evaluate the association between BRCA2 and AR genes and male breast cancer in Poland. We identified four frameshift mutations (11%) in exons 10, 11, 17 and 18, two of them were novel: 6495del3insC and 8457insA. Three missense unclassified variants (8%) of the BRCA2 gene were also identified. The frequencies of missense alterations were examined in a set of 200 chromosomes. No alteration of the AR gene was found. We did not observe much difference in clinicopathological features between carriers and non-carriers of BRCA2 mutations. Five of 37 patients (14%) had a family history of breast cancer, in one first- or second-degree relative, among the latter was one mutation carrier. The results of this study suggest that germ-line BRCA2 mutations account for rather small proportion of male breast cancer in Poland.

Abstract Breast cancer occurs rarely in men and risk factors for the disease include germline mutations of the BRCA2 gene. High frequency of allelic loss at the BRCA2 locus has been reported in sporadic breast tumors, but somatic mutations of BRCA2 are very rare. Here we report the first case of somatic BRCA2 mutation in male breast cancer with demonstrated loss of heterozygosity. We analyzed a series of 27 archival samples from male breast cancer patients for BRCA2 mutations and loss of heterozygosity at BRCA2 locus. The mutation analysis of BRCA2 gene was performed using SSCA‐HA and sequencing methods. PCR was used to detect LOH at 3 highly polymorphic microsatellite markers spanning BRCA2 region on 13q by comparing the allelic pattern in matched tumor and blood DNA samples. In this study LOH at the BRCA2 locus was observed in 82.6% of informative cases, confirming previous observations on high frequency of LOH affecting the BRCA2 region in male breast cancer. We identified 5 somatic BRCA2 mutations in a set of 23 sporadic male breast cancers (21%). Two silent and 1 missense alterations were novel BRCA2 variants. Here we also report first somatic frameshift BRCA2 mutation in male breast cancer 8138del5. In 3 tumors with somatic BRCA2 alterations, 1 missense, 1 silent and frameshift LOH at chromosome 13q12‐13 were detected and losses involved a wild–type allele of BRCA2 gene. © 2002 Wiley‐Liss, Inc.

AIM: Intrathyroid metastases are uncommon in cytology practice. We report a case of metastatic lesion in the thyroid from breast carcinoma which was recognized in a fine-needle aspiration (FNA) biopsy and confirmed by immunohistopathology. In addition, we provide an overview of the literature describing similar cases. STUDY DESIGN: The patient was a 54-year old woman with a large, multinodular goiter and bilaterally enlarged lymph nodes in the supraclavicular areas. Fourteen years earlier she had undergone radical mastectomy followed by chemio- and radiotherapy due to a breast carcinoma. RESULTS: FNA of the thyroid nodules showed a metastatic breast carcinoma and was followed by total strumectomy and lymphadenectomy. Histological reassessment of the surgical thyroid specimens as well as the neck lymph nodes revealed multiple breast metastases. This was strongly confirmed by immunohistochemical examinations, which revealed a positive staining for: CKMNF 116, CK7, CEA as well as for ER, PgR and HER2, and a negative staining for: CK20, thyroglobulin, TTF1, calcitonin, and chromogranin. CONCLUSION: Every new aggregate in the thyroid in patients with even a long-term history of cancer should be considered as potentially metastatic until proved otherwise. FNA could be helpful in the diagnosis of thyroid metastatic lesion, but it should be confirmed by immunohistopathology.

There are clinical and pathological factors associated with the clinical course of melanoma. These parameters allow us to predict survival times and establish a course of treatment. The aim of the study was to assess the significance of immunohistochemical markers in the progression of melanoma, and relate these findings to the influence of clinical and histological factors on survival time. In this study, archival histological material obtained from 50 melanoma patients operated on in the Great Poland Cancer Centre between 1990–1995 was analysed. Using immunohistochemistry we detected the presence of markers known to be important in the diagnosis of melanoma, including: HMB-45, PCNA, Ki-67, MMP-2, CD44 and nm23. Following this, univariate logistic regression was performed and clinical, histopathological and immunohistochemical data of statistical significance were correlated with survival time using the Cox nonparametric proportional hazard regression model. The results suggested that the most important prognostic factors correlating with survival time were: the presence of nm23 antigen (p = 0.0342) and the thickness of the melanoma, as measured by the Breslow method in mm (p = 0.0191). According to the univariate analysis there were correlations between patient death or survival and the histological type, Superficial Spreading Melanoma Malignum (SSMM) (p = 0.0187), regional lymphatic metastases (p = 0.0030) and positive Ki-67 results (p = 0.0282). Taken together, our results allowed us to conclude (a) that there was a correlation between survival time and nm23 antigen expression and the thickness of melanoma, as measured by the Breslow method in mm, (b) that there were correlations between patient survival or death and the histological type of Superficial Spreading Melanoma Malignum, regional lymphatic metastases and positive Ki-67, (c) that other parameters (age, gender, anatomical location of the melanoma, the presence of ulceration, lymphatic infiltration, the existence of satellites, and positive PCNA and MMP-2) showed no significant influence on survival.