Background: Gap junctions are intercellular channels composed of connexins, which mediate the direct passage of small molecules between neighbouring cells. They are involved in regulation of cell cycle, cell signalling, and differentiation, and probably invasion and metastasis. The role of connexins in the metastatic process is controversial, because some studies indicate that connexin expression is inversely correlated with metastatic capacity. In contrast, others demonstrate that connexins may be involved in metastasis. In addition, connexin status in breast cancer metastasis has not been widely studied. Methods: We evaluated by immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in primary breast tumours (PTs) and matched paired metastases to lymph nodes (MLNs). Results: In PTs, we observed predominantly cytoplasmic localisation of evaluated connexins, indicating alterations in connexin expression in breast cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in MLNs compared with PTs (p,0.00001 and p,0.001, for CX26 and Cx43, respectively). In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs. Furthermore, besides increased cytoplasmic staining, enhanced membranous localisation of Cx43, typical of normal cells, was found in MLNs. Additionally, membranous Cx26 expression appeared only in metastatic breast cancer cells. Conclusions: These findings suggest that connexins may contribute to the efficient metastasising of breast cancer to the lymph nodes.
The aim of the study was the evaluation of ER• and ERß expression in primary tumors and lymph node metastases of breast cancer as well as the assessment of the influence of preoperative chemotherapy on these receptors with regard to changes in morphological appearance of primary tumors and their metastases. Immunohistochemical examinations were conducted on surgically removed ductal invasive breast cancers and their lymph node metastases of 135 patients. Seventy-one patients were spared preoperative chemotherapy which was administered to other 64 patients. Primary breast cancers with preoperative chemotherapy showed lower mean percentage of cells with a positive reaction to ER• and ERß as compared to primary tumors without preoperative chemotherapy. There were positive correlations among primary tumors and lymph node metastases regardless of preoperative chemotherapy applied. On the other hand, ER• and ERß expressions were negatively correlated in primary tumors without chemotherapy in contrast to primary tumors after chemotherapy. Furthermore, it was observed that preoperative chemotherapy was responsible for significantly less damage to lymph node metastases of breast cancer in comparison to primary tumors. In cases of such advanced damage of primary tumors that made determination of estrogen receptor expression impossible, their evaluation was performed on metastases to regional lymph nodes. Although preoperative chemotherapy did not severely impair estrogen receptor expression, presented changes of their distribution are a sufficient reason for simultaneous labeling of estrogen receptors in both primary tumors and metastases due to various sensitivity to chemotherapy of primary cancers in comparison with involved lymph nodes.
Extensive application of new methods in histopathology has resulted in large quantities of data on molecular markers in different types of human tumors. The main purpose has been to obtain additional parameters for the characterization of various types of malignancy to give more precise information on their biological behavior. In this study we tested AgNOR and Ki-67 (MIB 1) staining in 39 ovarian mucinous tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and well-differentiated carcinomas at stage I of FIGO classification. In general, there was an increase in AgNOR median values from benign (1.83 +/- 0.8) to well-differentiated carcinomas (2.91 +/- 1.3) with an intermediate value in borderline (2.3 +/- 1.6). The lowest Ki-67 labeling index (LI) was found in benign cystadenomas (5.7% +/- 3.4%) and papillary mucinous cystadenomas (7.9 +/- 5.8%). In borderline tumors mean LI was 12.2 +/- 10.9% whereas well-differentiated carcinomas had higher LI (16.8 +/- 10.2%). There were no statistically significant differences between the evaluated tumors and techniques applied. In our opinion the AgNOR count and Ki-67 LI do not appear useful for assessing differences between borderline and well-differentiated mucinous ovarian tumors at stage I of clinical advancement.
The aim of the study was the quantitative assessment of nucleolar organizer regions (NORs) in the cells of preneoplastic and neoplastic endometrial lesions. Retrospective analysis included tissue material obtained from 87 patients with simple and complex hyperplasia with or without atypia and well-differentiated stage-I endometrial adenocarcinoma. Sections were made from routine paraffin blocks and stained with AgNO3. The mean number of AgNORs per cell was determined. The results obtained indicate that the evaluation of proliferative activity of cells expressed by AgNOR count can help in the distinction between atypical hyperplasia and well-differentiated adenocarcinoma, and thus can serve as a useful pathological criterion.
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