The retention of BCL-2 expression in the carcinomas and lymph node metastases may explain the resistance of colorectal tumours to chemotherapeutic treatment.
Because bcl-2 is believed to function by prolonging cell survival rather than by increasing proliferation, the presence of t(14; 18) in Hodgkin's disease (HD) would have profound implications for the pathogenesis of this neoplasm.
Continued expression of bcl-2 renders tumour cells resistant to drug-induced DNA damage by a mechanism different from classical mechanisms of drug resistance.
In this study, we have attempted a conclusive definition of the involvement of dominantly acting oncogenes (Bcl-1 and Bcl-2) and tumor suppressor loci (p53, 6q-) in 100 cases of B-CLL selected for their CD5 positivity and Rai's stage (0 to IV).
A strong negative relationship was observed, with 26 of 88 (30%) bcl-2-positive tumours being EGFR positive, compared with 16 of 23 (70%) bcl-2-negative tumours being EGFR positive (P = 0.001), raising the possibility that bcl-2 is an ER-regulated gene.
Thus, it is conceivable that bcl-2 protein may play a role in the oncogenesis of many hematolymphoid malignancies by interfering with programmed cell death, in concert with other oncogenes or tumor suppressor genes.
No difference with regard to bcl-2 and bcl-xL expression was observed between normal breast epithelium and tumor tissue or breast cancer and non-malignant epithelial cell lines.
No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity.
Tumor tissue was studied using immunohistochemical techniques and southern blot hybridization to detect immunoglobulin and bcl-2 gene rearrangement and in situ hybridization for the Epstein-Barr virus (EBV) genome.
However, a significant inverse correlation was seen between Bcl-2 expression and histological grade, Bcl-2 being absent in the majority of T1 undifferentiated tumors (grade-III carcinomas).
Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cytotoxic drugs and T cell-mediated cytotoxicity, respectively.
Several genes regulating apoptosis have been reported, including p53, one of the tumor suppressor genes, c-myc, one of the proto-oncogenes, and various kinds of Bcl-2 related genes.
We adapted flow cytometric techniques for measuring apoptosis and bcl-2 protein in solid tissues and concomitantly determined both parameters in 65 malignant solid neoplasms.
Previous cytogenetic and molecular genetic analyses indicate that SCLCs carry a number of chromosomal abnormalities and it would follow from the present results that the abnormal expression of bcl-2 may also play a role in the pathogenesis of SCLC, by increasing tumour mass through inhibition of apoptosis as previously proposed.
Although bcl-2 immunoreactivity was observed in all levels of primary cutaneous malignant melanomas, in 43% (9/21) of deep melanomas (Clark level > or = III), and 100% (7/7) of thick tumors (thickness > or = 4.00 mm), there was focal loss of immunoreactivity.
The bcl-2 protein is normally expressed in the regenerative crypt compartment of the colon, small intestine, and stomach, and has been found to be abnormally overexpressed as an early event in the dysplasia-carcinoma sequences of both ulcerative colitis-related and gastric neoplasias.
In patients treated either with adjuvant chemotherapy or tamoxifen, relapse-free survival at 5 years was significantly better among patients with bcl-2-positive tumors than in those with bcl-2 negative ones (P = 0.05 and 0.02, respectively).
Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.
The expression (or lack thereof) of bcl-2 may reflect the difference in the regulation of cell turnover between these tumors, or histogenetic differences.
With better understanding of the functional significance of these protein-protein interactions involving Bcl-2, Bax, and other members of the Bcl-2 protein family and with insights into the structural details of these interactions, it may eventually be possible to develop novel pharmacological agents that improve tumor responses to currently available anticancer drugs and that have other clinically relevant uses as well.