Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) proteolytic and vascular endothelial growth factor (VEGF) and receptor (VEGFR-1, VEGFR-2) angiogenetic capacity in serous borderline ovarian tumors (S-BOTs) for women with and without noninvasive implants. METHODS: The population was made up of 99 patients with S-BOTs as the primary diagnosis between 1985 and 1995, 44 of whom had noninvasive implants and 55 without implants. MMP-2, MMP-14, the type-2 tissue inhibitor of MMPs (TIMP-2), and VEGF and receptors (VEGFR-1, VEGFR-2) were examined by immunhistochemistry. RESULTS: Strong positive (+++) MMP-2 staining was found more frequently in women with primary S-BOTs and noninvasive implants (76%) than in those without implants (53%; p < 0.05). In contrast, staining for MMP-14 and TIMP-2 was not significantly different in the two groups. Furthermore, expression of MMP-2, MMP-14, and TIMP-2 was similar in primary tumors and in their noninvasive implants. Most tumors in both groups had no VEGF expression (84% in the noninvasive implant group and 82% in the group without implants), while moderate (++) to strong (+++) expression of VEGFR-1 and VEGFR-2 was detected in 79% and 94% of the two tumor groups, with no significant difference between the groups. CONCLUSIONS: Enhanced MMP-2 was seen in primary S-BOT with noninvasive implants. The presence of noninvasive implants was prognostic for disease-free survival.

Simultaneous bilateral breast carcinoma: Histopathological characteristics and CD44/catenin-cadherin profile.

AIMS: Family history of breast carcinoma, multicentric tumor foci in one breast, and in situ lobular carcinoma increase the risk of bilateral breast cancer (BBC), synchronous or metachronous. Synchronous tumors are designated as simultaneous breast carcinoma if they appear at the same time. The CD44 family and cadherin/catenin immunophenotype of this group of BBCs has not yet been evaluated. The aim of this study was to compare clinicopathological characteristics and immunohistochemical profiles of simultaneous BBC and corresponding lymph node metastases in eight patients. METHODS AND RESULTS: In toto 15 primary and 9 metastatic tumors were evaluated. The expression of CD44 variant isoforms, beta-catenin, E, P and N-cadherin were evaluated by immunohistochemistry. Rare types of breast carcinoma were frequent in this group of patients. There were 6 pleomorphic lobular, 5 invasive ductal of usual type, 3 atypical medullary carcinomas, 2 mucinous and one invasive micropapillary carcinoma. The expression CD44v6 was most frequent, followed by CD44v3-10, CD44v5, and CD44v3. CD44v4 was generally not expressed. E-cadherin was expressed in 80% primary tumors, 40% expressed N-cadherin, and 66% expressed P-cadherin. CONCLUSIONS: Generally, simultaneous carcinomas had different morphology and different immunophenotype. Each primary tumor was more similar to its corresponding metastatic tumor than to the contralateral primary tumor.

Immunohistochemical detection of p53--effect of fixation and methods of antigen retrieval.

Immunohistochemical detection of p53 in paraffin-embedded biopsy specimens has important diagnostic, prognostic and therapeutic applications. In this study the influence of four different methods of fixation on immunohistochemical staining have been investigated in breast tumor specimens. The application of antigen retrieval methods was examined and the results of two different methods of antigen unmasking were compared. Optimal results were obtained using samples fixed in 70% ethanol and Carnoy solution. Tissues fixed in neutral buffered formalin or Bouin solution required preliminary procedures for antigen unmasking. The technique of microwave antigen retrieval gave crisp, clear immunohistochemical staining for p53 in tissues fixed in neutral buffered formalin or Bouin solution. In conclusion, the findings in this study show that: 1. The most suitable fixatives for immunohistochemical detection of p53 are 70% ethanol and Carnoy solution. 2. Antigen retrieval procedures by microwave irradiation are recommended for tissues fixed in 10% neutral buffered formalin or in Bouin solution; this pre-treatment improves the quality of the immunohistochemical reaction and decreases the possibility of false negative results. 3. The cytoplasmic accumulation of p53 should be accepted as a fact, not as a result of poor fixation and should be assessed in parallel with the nuclear reaction.

Expression of c-erbB-2 oncogene and p53 tumor suppressor gene in benign and malignant breast tissue: correlation with proliferative activity and prognostic index.

The expression of c-erbB-2 oncogene and p53 tumor suppressor gene was studied in methacarn-fixed, paraffin-embedded biopsy specimens from 58 benign breast lesions and 129 sporadic breast carcinomas, using the supersensitive monoclonal antibodies CB 11 and BP 53-12-1 and the biotin-streptAvidin-amplified methodology. None of the benign lesions studied, which included 36 fibrocystic lesions with mild or florid epithelial hyperplasia, 12 fibrocystic lesions with ADH or ALH and 10 fibroadenomas, demonstrated membrane staining for c-erbB-2 or nuclear immunoreactivity for p53. Overall, 48.06% of primary breast carcinomas showed membrane expression of c-erbB-2, while 28.68% were p53 positive. Those showing p53 immunoreactivity displayed a nuclear and/or cytoplasmic staining type. A significant correlation was seen between c-erbB-2 and p53 expression (r = 0.213, p < 0.05), as well as between c-erbB-2 status and PSNA score (r = 0.221, p < 0.05). In addition, c-erbB-2 and p53, separately or in combination, correlated significantly with the prognostic index. In conclusion, immunohistochemistry of c-erbB-2 and p53 immunohistochemistry allows a better definition of intraductal proliferative lesions and assists in the differentiation between ADH and DCIS. It provides additional clues with regard to the biologic behavior of invasive ductal carcinomas (NOS and medullary).