Expression and significance of survivin in colorectal high grade and low grade adenomas.

We examined immunohistochemically the expression pattern of a potential tumor biomarker survivin in a panel of 116 tubular adenomatous polyps to determine its association with clinicomorphological parameters such as age of patients, size of polyps, degree of dysplasia and polyp localization. In each section, the subcellular localization of survivin antigen and the intensity of staining were assessed. Overall, survivin was expressed in 90 cases (77.6%). Cytoplasmic positivity was observed in 46/116 cases (39.7%), while nuclear and combined nuclear and cytoplasmic reaction in 44/116 cases (37.9%). High grade dysplasia was diagnosed in 52 cases (44.8%) and low grade dysplasia in 64 cases (55.2%). Statistical analysis revealed a significant correlation between subcellular survivin localization and the degree of dysplasia, size of polyps and colon localization. On the other hand, survivin expression pattern did not correlate with the age of patients. Statistically significant trend was confirmed between intensity of survivin immunoreaction and tumor size and dysplasia grade, and also the trend between negative/strong survivin intensity and polyp localization. Another statistically significant association was found between the degree of dysplasia and the size of polyps. Our findings revealed that survivin is frequently expressed in different subcellular compartments of adenoma cells. Our recent results suggest that the nuclear and combined nuclear and cytoplasmic survivin localizations are strongly associated with poor prognostic parameters in the assessment of colon adenomas. Thus, survivin may represent a promising biomarker in immunohistochemical evaluation of these lesions.

Relationship of mismatch repair proteins and survivin in colon polyps and carcinomas.

Mismatch repair genes (MMR) play an essential role in DNA repair. MMR mutations predominantly in MLH1, MSH2, MSH6, PMS2, and rarely in PMS1, may cause the production of abnormally short or inactivated proteins. The antiapoptotic protein survivin functions in the inhibition of apoptosis, regulation of cell division and also enhances angiogenesis. Both MMRP and survivin are considered to be powerful prognostic parameters. This study was designed to determine the relationship between MMRP and survivin in colon lesions. The study included 113 cases of colon carcinoma and 51 cases of colon polyps. Survivin expression and MMRP status were assessed by immunohistochemistry. In each section, expression, intensity of immunostaining and percentage of labeled cells were analyzed. In carcinomas, immunoreaction was detected in 100/113 cases for MLH1 (88.5%), 112/113 cases for MSH2 (99.1%), 110/113 cases for MSH6 (97.3%), and 103/113 cases for PMS2 (91.2%). Survivin was shown in 47/113 cases (41.6%). The statistical analysis confirmed a significant correlation between the expression of MMRP and survivin in the assessed parameters. All 51 polyp samples were positive for MLH1, MSH2, MSH6 and PMS2. Only 8 of those (15.7%) were positive for survivin. Statistically significant differences were observed between the expression of MMRP and survivin. In conclusion, this study revealed that MMRP may suppress the antiapoptotic function of survivin through p53 inactivation of its promoter in grade 1 and grade 2 colon carcinomas.

Unusual occurrence of rare lipid-rich carcinoma and conventional invasive ductal carcinoma in the one breast: case report.

A 56-year-old woman noticed a palpable mass in her left breast during self-examination. Patient was admitted to our hospital and malignant bifocal tumour was diagnosed by ultrasonography, digital mammography, magnetic resonance, and core-cut biopsy. The patient underwent planned conservative surgery (biquadrantectomy) with a sentinel node examination, but after results of the frozen section with positive resection margins and positive sentinel lymph nodes subsequent mastectomy with axillary lymph node dissection were realized. Histology in the resection specimen revealed two isolated and distinct tumours. One of the lesions represented conventional invasive ductal carcinoma of histological grade 3, and the second tumour was evaluated as invasive lipid-rich carcinoma, containing tumour cells with clear and foamy cytoplasm. Lipids in neoplastic cells were detected by Oil Red O staining and ultrastructural examination. Immunohistochemical analysis of both carcinomas was almost identical with negative steroid receptors, positive staining of HER-2, and p53 and with high proliferation activity (Ki-67). Mastectomy specimen contained residual foci of invasive ductal carcinoma and dissected axillary lymph nodes were free of metastasis. Patient underwent first cycles of chemotherapy with paclitaxel and Herceptin together with local radiotherapy and two month after surgery is without any evidence of the disease.

Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas.

BACKGROUND: The tumor suppressor gene p53 is a key regulator of cell division and/or apoptosis. Survivin is a multifunctional member of the inhibitor of apoptosis family. Survivin and p53 represent diametrically opposed signals that influence the apoptotic pathway. MATERIAL/METHODS: To determine the role of p53 and survivin in basal cell carcinoma (BCC), we evaluated the expression pattern of both proteins with regard to the percentage of positively immunostained tumor cells, the intensity of staining, and subcellular localization among 31 subjects with BCC. RESULTS: Overexpression of p53 protein was found in 28 of 31 cases (90.3%), whereas survivin accumulation was seen in 27 (87.1%). For p53, moderate and/or strong immunoreactivity was seen in 20 of 28 cases (71.4%), and 26 of 28 cases (92.9%) showed more than 25% reactive tumor cells. Nuclear p53 staining was detected in 23 of 28 cases (82.1%), whereas combined nuclear and cytoplasmic localization was found in only 5 of 28 cases (17.9%). Survivin revealed mild intensity of immunoreaction in 22 of 27 cases (71%), and 25 of 27 cases (92.6%) showed less than 25% labeled tumor cells. Combined nuclear and cytoplasmic survivin localization was present in 26 of 27 cases (96.3%). Statistically significant differences were detected in the assessed expression parameters between those proteins. CONCLUSIONS: Our results suggest that overexpression of wild type p53 protein may suppress the expression of survivin and its antiapoptotic activity in BCC cells.