The aim of this study was the analysis of Ki-67, Bcl-2 and Bak expression in primary tumor and axillary lymph node metastases of breast cancer as well as an attempt to assess preoperative chemotherapy influence on the mentioned markers with regard to changes in the morphological appearance of the primary tumor and its metastases. Immunohistochemical examinations of Ki-67, Bcl-2 and Bak expression were conducted on sections collected from 135 patients treated surgically on invasive ductal breast cancer. Sixty-four of these patients were administered preoperative chemotherapy, whilst on 71 patients the surgery was performed without initial chemotherapy. In the group of patients without preoperative chemotherapy positive correlation in Ki-67 and Bcl-2 expression between primary tumors and lymph node metastases (p<0.0001, r=0.707; p<0.0001, r=0.604, respectively) was observed. In the group of patients after chemotherapy positive correlation between primary tumors and lymph node metastases in case of Bcl-2 and Bak proteins (p<0.04, r=0.424; p<0.02, r=0.478, respectively) was observed. It was also found that preoperative chemotherapy has an influence on the expression of proteins connected with proliferation and apoptosis and thus, it can influence neoplastic process biology. It does not have any significant impact on the proapoptotic Bak protein expression either in primary tumor or in lymph node metastases of breast cancer. However, it is related to lower expression of antiapoptotic Bcl-2 protein (p<0.0005) and of Ki-67 proliferation marker (p<0.03) in primary tumors, which indirectly indicates a beneficial influence of preoperative chemotherapy on the primary tumor. Concurrently, the influence of neoadjuvant therapy on lymph node metastases seems to be relatively small, which can limit its effectiveness.

Progression of numerous neoplasms could involve alterations of gap junction channels composed of connexins (Cxs). Disorders of expression and cellular displacement of Cxs were also found in endometrial cancer. Gap junctional intercellular communication can be regulated by wide array of agents, for instance, growth factors, oncogenes, and steroid hormones. Nevertheless, expressions of Cxs and progesterone receptor (PR) were not compared in human tissues. This study focused on assessment of expression of estrogen receptor alpha (ERalpha) and PRs in relation to the expression of Cx26 and Cx43 in 88 cases of endometrial cancer and analysis of these proteins' expression in comparison with anatomoclinical features. Positive ERalpha and PR nuclear staining was present in 66 (75%) and 60 (68.2%) of all studied tumors, respectively. Positive correlation was found between expression of PR and histopathologic type of tumor (P = 0.026), and negative correlation was drawn with grading (G) (P = 0.002). There were positive reactions to Cx26 and Cx43 of mainly cytoplasmic location in 60 (68.2%) and 66 (75%) of studied cancers, respectively. Progesterone receptor expression correlated negatively with Cx26 in endometrial cancers (P = 0.016, r = -0.256). Moreover, ERalpha expression positively correlated with PR expression (P < 0.001, r = 0.678). On the ground of our findings, disorders of Cx expression and altered distribution pattern occur during endometrial carcinogenesis, and it seems that PR could participate in this fact. Loss of functional gap junctions may occur because of the aberrant expression and localization of Cx26 and Cx43 in endometrial cancer.

During carcinogenesis, loss of intracellular cohesion is observed among cancer cells with altered expression of such adhesion molecules as E-cadherin and beta-catenin, and aberrant expression and cellular location of intercellular gap junction proteins-connexins. The aim of this study was to evaluate immunohistochemically the expression and relationship between E-cadherin and beta-catenin, and the connexins Cx26 and Cx43 in 86 endometrioid adenocarcinomas. The aberrant cytoplasmic translocation of the studied proteins was a predominant finding, whereas only a minority of cases showed normal, nuclear beta-catenin labeling or membranous distribution of the remaining molecules. E-cadherin was positively and significantly associated with beta-catenin (P=0.001, r=0.366), as was Cx26 with Cx43 (P<0.001, r=0.719), E-cadherin with Cx26 (P<0.001, r=0.413), and E-cadherin and Cx43 (P<0.001, r=0.434) in all cancers. A subgroup of endometrioid adenocarcinomas (FIGO IB+II) exclusively showed a positive significant association between the expression of beta-catenin and Cx26 (P=0.038, r=0.339). In addition, there were significantly more beta-catenin-positive carcinomas among superficially spreading cancers (FIGO IA) than among deeper invading neoplasms (FIGO IB+II) (P=0.056). The altered location of the studied proteins indicates impairment of their physiological functions. In particular, normal membranous distribution of E-cadherin and connexins is lost and replaced by abnormal cytoplasmic accumulation in most cancers, and thus intercellular ties are expected to be weakened and loosened as a consequence. In contrast, the lack of relationship between beta-catenin and connexins, E-cadherin seems to be closely associated with the expression of Cx26 and Cx43 in endometrioid adenocarcinomas.

Disturbances in expression of apoptosis-associated proteins take part in the development and progression of many human malignancies. The aim of this study was the assessment of correlations among proteins involved in apoptosis-Bcl-xL, Bax, and p53-as well as relationships of these proteins with selected clinicopathological features in oral squamous cell carcinoma. Consequently, we examined by immunohistochemistry, using the avidin-biotin-peroxidase method, Bcl-xL, Bax, and p53 expression in 56 samples of primary oral squamous cell carcinoma and in 22 matched pairs of primary and metastatic tumors. The evaluation of immunostaining of Bcl-xL, Bax, and p53 was analyzed in 10 different tumor fields, and the mean percentage of tumor cells with positive staining was evaluated. The significance of the associations was determined using Spearman correlation analysis and the chi-square test. We found positive Bcl-xL, Bax, and p53 immunostaining in 44.6%, 28.6%, and 58.9% of the studied primary tumors and in 63.6%, 45.5%, and 72.7% of lymph node metastases, respectively. Analysis of associations among studied proteins revealed positive correlation between Bcl-xL and Bax in primary tumors (P<0.03, r=0.307). Statistically significant relationship between p53 expression in primary oral cancers and its expression in lymph node metastases (P<0.02) as well as increased expression of Bcl-xL, Bax, and p53 in metastatic sites compared with primary tumors could indicate an association of these proteins with oral cancer progression and development of metastases. Moreover, we suppose that knowledge about heterogeneity between primary and metastatic tumor might help to understand mechanisms of oral cancer progression.

Abstract:Alterations of gap junctional intercellular communication appear to play a role in the development and progression of cancer. Gap junction channel is composed of two connexons -hexameric units formed of transmembrane proteins called connexins (Cxs). The aim of the study was to evaluate the expression and localization of Cx26 in 73 cases of endometrial cancers and to estimate the relationships between expression of this protein and selected anatomoclinical features. The control group consisted of 20 sections of normal endometrium in various menstrual cycle phases, obtained from premenopausal women. In the normal endometrium punctate, membrane-associated immunoreactivity for Cx26 was observed. 54 of 73 endometrial cancers showed Cx26 expression, but 46/54 (85%) immunopositive sections revealed cytoplasmic localization for Cx26 with granular or occasionally diffuse immunostaining pattern. In addition, part of Cx26-positive tumours showed mixed: cytoplasmic and membranous staining pattern and focally also nuclear or perinuclear immunostaining was present. In 21/54 (39%) of Cx26-positive cases weak staining pattern was seen, however in 33/54 (61%) cancers strong reaction was noted. We did not find relationship between Cx26 expression and patients' age, histological type of cancer and histological grade, nevertheless we observed positive association between Cx26 expression and tumour size (p=0.037). In conclusion, our results suggest that transformed malignant cells continue to produce Cx26, which are probably not assembled into functional gap junction channels, but could still play other roles in endometrial cancer cells.