The relationships between PD-L1 expression, CD8+ TILs and clinico-histomorphological parameters in malignant melanomas.

INTRODUCTION: Malignant melanomas (MM) are often connected with the expression of PD-L1 protein and the presence of tumor-infiltrating lymphocytes (TILs), however, their impact on prognosis remains controversial. Due to their supposed clinical significance and lack of convincing data, we decided to establish the relationships between CD8 + TIL count, PD-L1 level and certain clinical and histopathological parameters in patients with malignant melanoma, especially those associated with unfavorable prognosis. MATERIALS AND METHODS: We performed immunohistochemistry for PD-L1 and CD8 on 56 formalin-fixed paraffin-embedded specimens from patients with cutaneous and metastatic malignant melanomas. PD-L1 expression levels were determined by immunohistochemistry (clone 28-8) and subsequently the tumor proportion scores (TPS) were evaluated. CD8 + TIL expressions were classified as either grade 0, 1+, 2+ or 3+, based on the density and distribution of the infiltrating lymphocytes. RESULTS: The PD-L1 expression was detected in 20 out of 56 cases (35,71 %). The expression of PD-L1 on tumor cells was significantly increased with higher TILs infiltration in the tumor microenvironment (p = 0,038). Lower TIL score corresponds with poor prognostic clinicopathological parameters such as higher number of mitotic figures (p = 0,005), Clark's level (p = 0,007) and Breslow's depth (p = 0,010). CONCLUSIONS: Our results suggest a favorable prognostic value for CD8 + TIL infiltration. Moreover, TIL density was strongly correlated and geographically associated to PD-L1 expression. This analysis provides more insight into the role of TIL count and PD-L1 level in MM and their relationship with each other and association with other prognostic indicators.

Expression of Ki-67, Bcl-2, Survivin and p53 Proteins in Patients with Pulmonary Carcinoma.

Apoptosis is the fundamental process necessary for eliminating damaged or mutated cells. Alterations in the apoptotic pathway appear to be key events in cancer development and progression. Bcl-2 is the key member of the Bcl-2 family of apoptosis regulator proteins with anti-apoptotic effects. Survivin acts as an inhibitor of apoptosis as well and has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor proteins, prevents tumor formation through cell cycle blocking and eliminates damaged cells via the activation of apoptosis. The Ki-67 protein is a cellular marker for proliferation. To investigate the possible interactions of the aforementioned proteins, we examined their expression in 76 patients with diagnosed lung cancer using immunohistochemical visualisation. Ki-67 protein was expressed in the cancer cells of all patients with small cell lung cancer (SCLC). We found a negative correlation between survivin and p53 expression. A decreased intensity of survivin expression and fewer cells positive for survivin (66.7%) in SCLC in comparison with other lung cancer types (98.0%) was detected. Reversely, expression of Bcl-2 was found in more than 90% of cases with SCLC. We hypothesize that high expression and intensity of Bcl-2 protein could be a factor behind a bad prognosis in SCLC.

Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment.

The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment.

Correlations of survivin expression with clinicomorphological parameters and hormonal receptor status in breast ductal carcinoma.

The antiapoptotic protein survivin is widely expressed in most human cancers, including carcinomas of the breast. It is rarely detected in corresponding normal adult tissues. Therefore, survivin comes into the limelight as a promising diagnostic biomarker and prognostic parameter. Immunohistochemically, we examined the expression of this protein in 126 cases of ductal breast carcinoma to determine the association with clinicomorphological parameters such as age of patients, grade, stage and size of the primary tumor, lymph node metastasis, vascular invasion as well as estrogen and progesterone status. In each section, the subcellular location of survivin antigen, the intensity of staining and the percentage of labeled cells were assessed. Overall, survivin was expressed in 111 cases (88.1%). The statistical analysis revealed a significant correlation between the nuclear location of survivin and tumor grade 3. Furthermore, a significant relation was also found between vascular invasion and nuclear and combined nuclear and cytoplasmic survivin expression, together with a higher intensity of immunoreaction. However, no significant correlations were shown with other clinicomorphological parameters, such as stage and size of the tumor, lymph node metastasis, estrogen and progesterone receptors and age. Our findings revealed that survivin was frequently overexpressed in carcinoma cells, where it was present in different subcellular compartments. The nuclear positivity of survivin or combined nuclear and cytoplasmic expression was shown to be a poor prognostic parameter in ductal breast carcinoma.

Survivin: a promising biomarker in breast carcinoma.

The antiapoptotic protein survivin can be detected in most types of malignant tumors, but it is rarely expressed in corresponding normal adult tissues. Therefore, survivin appears to represent a promising diagnostic biomarker. We examined survivin expression in 13 cases of normal breast tissue, 38 cases of fibroadenomas and 80 cases of breast carcinomas by immunohistochemical staining using anti-survivin antibody (DAKO, Clone 12C4). In each section, the intensity of staining, percentage of labeled cells, and the subcellular location of survivin antigen were assessed. Survivin was detected in 4/13 cases of normal breast tissue (30.7%), in 28/38 cases of fibroadenomas (73.7%), and in 67/80 cases of carcinomas (83.8%). Normal breast tissue showed cytoplasmic positivity only. In fibroadenomas, 19 cases (50.0%) revealed cytoplasmic reaction, and in 9 cases (23.7%), small foci of cells with combined nuclear and cytoplasmic location were identified. In carcinomas, cytoplasmic staining was found in 12/80 cases (15.0%), nuclear staining in 10/80 cases (12.5%), and combined cytoplasmic and nuclear staining in 45/80 cases (56.3%). Subcellular location of survivin between benign and malignant lesions revealed significant differences (p<0,001). Our findings point at practical use of survivin detection. We confirm the importance of nuclear staining of survivin antigen in breast carcinoma, which seems to be a notable diagnostic marker for estimation of the degree of neoplasia.

[Perforating folliculitis. Case report and differential diagnosis]. / Folliculitis perforans kazuistický prípad a diferenciálna diagnostika choroby.

A 26-year-old woman suddenly noticed an onset of disseminated papular exanthema during her institutional treatment for alcohol abuse. After 9 weeks of slowly progressive course a dermatologist was consulted, who suggested a diagnosis of pityriasis lichenoides. Skin biopsy revealed cystical enlargement of hair follicles that were filled up with keratinous and parakeratotic masses interspersed with particles of fragmented collagen. Numerous inflammatory cells were present within the lesion. Many focal perforations of infundibular epithelium draining a cellular debris were prominent. Severely disturbed follicles were engulfed by giant cell inflammatory infitrate containing remnants of collagen and elastic fibers. Considering all the histopathologic findings and clinical course, the case was finally diagnosed as perforating folliculitis, a distinct type from the family of perforating dermatoses.

Expression of anti-apoptotic protein survivin and tumor suppressor p53 protein in patients with pulmonary carcinoma.

BACKGROUND: Survivin is one of the inhibitors of the apoptosis gene family that has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor genes; prevents tumor formation through cell cycle blocking and eliminates damaged cells via activation of apoptosis. OBJECTIVE: To investigate the possible regulation of survivin by p53, we examined the expression of both proteins in 67 patients with diagnosed lung cancer using immunohistochemical visualization. RESULTS: Survivin was predominantly expressed in both nucleus and cytoplasm, whereas p53 was expressed in the nucleus. There was a negative correlation between survivin and p53 expression. A decreased intensity of expression and fewer cells positive for survivin in small cell lung cancer in comparison with other lung cancer types were detected. There was no significant difference in the intensity of expression and the number of cells positive for p53 between small cell and non-small cell lung cancer types. CONCLUSION: The present study suggests that survivin expression, as opposed to that of p53, is decreased in small cell lung cancer, which may differentiate this cancer from other lung cancer types other types.

[Diagnostic procedures in skin adnexal tumours]. / Diagnostika adnexálnych tumorov koze.

From histogenetic, morphologic and immunohistochemical point of view the authors try to make possible algorithms that can be employed in a routine diagnosis of adnexal skin tumours. They stress the importance of knowledge of clinical data necessary for orientation classification of tumour skin lesions after biopsies. The authors translated their obtained data into survey tables to be used as guidelines in a routine bioptic practice.