Investigation of Human Cytomegalovirus and Human Papillomavirus in Glioma.

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics (p > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.

Investigation of simian virus 40 (SV40) and human JC, BK, MC, KI, and WU polyomaviruses in glioma.

The gliomagenesis remains not fully established and their etiological factors still remain obscure. Polyomaviruses were detected and involved in several human tumors. Their potential implication in gliomas has been not yet surveyed in Africa and Arab World. Herein, we investigated the prevalence of six polyomaviruses (SV40, JCPyV, BKPyV, MCPyV, KIPyV, and WUPyV) in 112 gliomas from Tunisian patients. The DNA sequences of polyomaviruses were examined by PCR assays. Viral infection was confirmed by DNA in situ hybridization (ISH) and/or immunohistochemistry (IHC). The relationships between polyomavirus infection and tumor features were evaluated. Specific SV40 Tag, viral regulatory, and VP1 regions were identified in 12 GBM (10.7%). DNA ISH targeting the whole SV40 genome and SV40 Tag IHC confirmed the PCR findings. Five gliomas yielded JCPyV positivity by PCR and DNA ISH (2.7%). However, no BKPyV, KIPyV, and WUPyV DNA sequences were identified in all samples. MCPyV DNA was identified in 30 gliomas (26.8%). For GBM samples, MCPyV was significantly related to patient age (p = 0.037), tumor recurrence (p = 0.024), and SV40 (p = 0.045) infection. No further significant association was identified with the remaining tumor features (p > 0.05) and patient survival (Log Rank, p > 0.05). Our study indicates the presence of SV40, JCPyV, and MCPyV DNA in Tunisian gliomas. Further investigations are required to more elucidate the potential involvement of polyomaviruses in these destructive malignancies.

Utility of the immunohistochemical analysis of DNA mismatch-repair proteins in endometrial hyperplasia.

The utility of the expression lack of DNA mismatch-repair (MMR) proteins in the detection of Lynch syndrome in endometrial hyperplasia as precursor lesion of endometrial carcinoma has not been well-established. The study investigated the immunoexpression pattern of MMR proteins in endometrial hyperplasia from Tunisian patients. We carried out a retrospective study of 60 endometrial hyperplasias diagnosed among Tunisian patients. Expression of MLH1, MSH2, MSH6, and PMS2 proteins was performed by immunohistochemistry on whole-slide sections of archival tissues. Analysis of MLH1 promoter methylation and microsatellite alterations was conducted in appropriate cases. Microsatellite instability screening was assessed using the Bethesda panel, including BAT25, BAT26, D17S250, D2S123, and D5S346 markers. Expression of MMR proteins was observed in all hyperplasias without atypia as well as in 27 out of 29 atypical hyperplasias. Only two atypical hyperplasias exhibited expression loss of MMR proteins. A single case revealed MSH6 expression lack. Expression loss of MLH1 and PMS2 was identified in another atypical hyperplasia and was associated with hypermethylation of MLH1 promoter. This patient had no familial history of endometrial cancer at the diagnostic time. The two deficient MMR cases showed microsatellite stable pattern. In conclusion, only two endometrial hyperplasias displayed an altered pattern of MMR expression. Our results suggest the limited utility of the immunohistochemical analysis of MMR protein in the early detection of Lynch syndrome in Tunisian patients diagnosed with endometrial hyperplasias. Multicenter studies with larger sample size are needed to more explore these findings.

Prognostic significance of MGMT methylation and expression of MGMT, P53, EGFR, MDM2 and PTEN in glioblastoma multiforme.

The study investigated the pattern of MGMT promoter methylation and the expression of MGMT, P53, EGFR, MDM2 and PTEN proteins in glioblastomas multiforme (GBM) and evaluated their prognostic significance. We carried out a retrospective study of 80 GBM. Expression of MGMT as well as of P53, EGFR, MDM2 and PTEN was investigated by immunohistochemistry. MGMT promoter methylation was investigated by methylation specific-PCR of bisulfite-treated DNA. Twenty-five GBM exhibited MGMT expression. Methylation of MGMT promoter was detected in 35.1% of cases. No significant concordance was reported between MGMT promoter methylation and protein expression (κ=-0.047, p=0.11). MGMT promoter methylation was significantly associated only with PTEN expression (p=0.001): no other significant association was identified with clinical parameters as well as with expression of P53, EGFR and MDM2 (p >0.05). Tumor recurrence was significantly associated with unmethylated MGMT promoter (p=0.01) but not with MGMT expression (p=0.51). Recurrence-free survival (RFS) was significantly better among patients with methylated MGMT promoter (log rank, p <0.0001) and PTEN expression (log rank, p=0.025) but not with MGMT expression (log rank, p=0.308). As well, using univariate analysis, MGMT promoter methylation (p=0.001) and PTEN expression (p=0.044) were significantly associated with RFS. In multivariate analysis, only MGMT promoter methylation was significantly associated with RFS (p=0.003). Together, our findings support that MGMT protein expression doesn't reflect the MGMT promoter methylation status. Furthermore, MGMT promoter methylation remains a useful prognostic marker in Tunisian patients with GBM. PTEN expression could be a potential prognostic marker of this tumor.

Signification of forkhead box A1 (FOXA1) expression in thyroid cancers.

BACKGROUND: Forkhead box A1 (FOXA1) plays an important role in several tumors. This study investigated the potential role of FOXA1 expression in thyroid tumors. We conducted a retrospective study of 110 thyroid lesions and tumors diagnosed during 1995-2018. The expression of FOXA1 was analyzed by immunohistochemistry on archival material. RESULTS: No FOXA1 immunostaining was observed in all cases of Graves' disease, Hashimoto's disease, multi-nodular goiter, and adenoma. FOXA1 expression was absent as well in all papillary and follicular carcinomas, Hurthle cell carcinoma, and undifferentiated sarcoma. Only three anaplastic carcinomas exhibited focally FOXA1 staining. However, FOXA1 was expressed in all medullary carcinomas. No significant correlation was found with all clinicopathological features (p > 0.05 for all). The pattern of FOXA1 staining was similar to that of calcitonin and chromogranin A (p = 0.04 and p = 0.003, respectively). CONCLUSIONS: FOXA1 is expressed mostly in all medullary thyroid carcinomas. Hence, FOXA1 could serve as an additional marker for refining the diagnosis of medullary thyroid carcinoma.