CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization.

INTRODUCTION: CDKN2A/B homozygous deletion is one of the defining features of grade 4 in IDH-mutant astrocytic tumours. AIM: To evaluate CDKN2A/B-deletion in IDH-mutant astrocytic tumours and its clinicopathological impact. MATERIALS AND METHODS: CDKN2A/B-deletion was evaluated by Fluorescence in-situ hybridisation (FISH) and interpreted by two recently accepted methods. RESULTS: Eighty-three out of 94 cases (histologically-grade 2: 3, grade 3: 46, grade 4: 34) were interpretable on FISH. Concordant CDKN2A/B-deletion was observed in 71% (27/38) of lower-grade tumours (n = 49) and 90% (27/30) of histological grade 4 tumours (n = 34). Both the interpretation methods showed good agreement (Kappa = 0.75). CDKN2A/B-deletion showed an inverse correlation for < 10% MIB-1 labeling index (p = 0.01) while that by method-2 showed a significant correlation for grade 4 (p = 0.02). No significant correlation was observed for any other clinicopathological parameters. Twenty-four patients showed progression/recurrence (including deaths), and no significant difference in frequency of CDKN2A/B deletion was observed among cases with disease progression across different histological grades. CONCLUSIONS: CDKN2A/B-deletion was observed across all the histological grades of IDH-mutant astrocytic tumours, expectedly more in the higher grade. FISH, as a method, can be used for the detection of CDKN2A/B homozygous deletion, when there is concordant interpretation.

MGMT gene promoter methylation and its correlation with clinicopathological parameters in glioblastomas.

BACKGROUND: MGMT (O6-methyl guanine DNA methyl transferase) promoter hypermethylation is a prognostic and predictive biomarker for glioblastomas (GBM). AIMS: To evaluate the frequency of MGMT methylation status in a single institute series of 134 GBMs and correlate it with clinical (age, sex, location, survival) and other molecular parameters [such as p53 expression, alpha thalassemia/mental retardation syndrome X-linked (ATRX) expression, isocitrate dehydrogenase (IDH) 1R132H mutation, and epidermal growth factor receptor (EGFR) gene amplification]. RESULTS: One hundred and thirty-four GBMs were evaluated by methylation-specific polymerase chain reaction (MSP) for MGMT promoter methylation status. The results were correlated with the above mentioned clinicopathological parameters. MGMT gene promoter methylation was identified in 49.2% (66/134) GBMs, and was significantly associated with IDH1R132H mutation (14/66; 21%; P - value, 0.01) and ATRX loss (15/66; 23%; P - value, 0.01). Confluent necrosis was found to be significantly associated with MGMT unmethylation status (P - value: 0.002). Multivariable logistic regression analysis showed confluent necrosis as a single independent predictor (odds ratio [OR], 2.5; confidence interval [CI], 1.0-5.8; P - value, 0.04) of MGMT unmethylation status among all the parameters studied. CONCLUSIONS: The frequency of MGMT promoter methylation in GBMs was 49.2%, which was significantly associated with IDHR132H mutation and ATRX loss. In addition, the presence of confluent necrosis was significantly associated with MGMT unmethylation and was found to be an independent predictor of the same.

Diffuse glioma - Rare homozygous IDH point mutation, is it an oncogenetic mechanism?

Isocitrate dehydrogenase (IDH1/IDH2) mutations in gliomas of WHO grade II/III and secondary glioblastoma are almost always heterozygous missense mutations. Here, we report an extremely rare case of homozygous IDH1R132H mutation in a recurrent WHO grade III anaplastic astrocytoma. The authors here also review the relevant literature for the possible metabolic impact of homozygous IDH1/2 mutations in the gliomagenesis.

Triple-Negative Breast Cancer: A Comprehensive Study of Clinical, Histomorphological, and Immunohistochemical Features in Indian Patients.

Triple-negative breast cancers (TNBCs) are characterized by negative expression for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors. Although the majority of basal-like breast cancers (BLBCs) diagnosed based on gene expression profiling belong to the TNBC group, both entities are not synonymous. Core BLBCs are TNBCs, which are positive for basal cytokeratin (CK) and/or epidermal growth factor receptor (EGFR). We aimed to study and correlate a TNBC cohort for various histomorphological features and immunohistochemical (IHC) profile in Indian patients. We studied 205 naïve TNBCs for histopathological features, which were further evaluated for basal CKs-namely, CK5/6, CK14, CK17-and EGFR expression to classify them as core BLBCs, using criteria of any basal CK and/or EGFR positivity and 7-negative phenotype (7NP). Among 205 TNBCs, 91% of cases were core BLBCs, and absence of ductal carcinoma in situ (DCIS) was significantly associated ( P = .014) with core BLBC. Geographic necrosis was correlated with expression of CK17 ( P = .002) and EGFR ( P = .038). A ribbon-like trabecular pattern and absence of DCIS were associated with CK17 ( P = .0002 and P = .043, respectively) and CK14 ( P = .04 and P = .0008, respectively). TNBC is a heterogeneous subgroup with adverse clinicopathological features, and many of them show significant correlation with basal CKs. TNBCs cannot be classified as core BLBC or 7NP based on morphological features, except absence of DCIS. However, this study illustrates the heterogeneity in TNBCs on the basis of IHC markers.