Mutant IDH 1 Expression in Non-Neoplastic And Neoplastic NonMelanoma Epithelial Skin Lesions; IHC Expression And Clinicopathological Relations
Journal Title: IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) - Year 2017, Vol 16, Issue 10
Abstract
Background: Cellular metabolism is known to be altered in cancer cells which switch to glycolysis and lactate fermentation for ATP production (Warburg Effect) providing a growth advantage for cancer cells. The “Warburg Effect” is mediated by dysregulation of metabolic enzymes. Isocitrate Dehydrogenase 1 (IDH1) is one of the metabolic enzymes; it catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, with subsequent NADPH/NADH release. Recently, IDH1 mutation was discovered to be involved in multiple human cancers, such as adult gliomas, acute myeloid leukemias, prostate cancer, and colorectal cancer. This study aim to evaluate IHC expression IDH1 mutation in non-neoplastic and neoplastic non- melanoma epithelial skin lesions and correlate its expression with clinicopathological features of patients. Materials and methods: Fifty patients were included in the study, twenty patients had non-neoplastic skin lesions (10 cases seborrheiac keratosis & 10 cases actinic keratosis) and thirty patients had neoplastic skin lesions (15 cases SCC & 15 cases BCC). Additionally, 5 control skin biopsies were taken from mastectomy specimens. Adequate tissue in paraffin blocks for IHC using IDH1-R132Hspecific antibody were assessed for IDH1 mutations. Results: Positive mutant IDH1 IHC staining showed a cytoplasmic/nuclear staining. Increased IDH1 mutant expression was noticed in neoplastic non-melanoma compared to non-neoplastic skin lesions. IDH1 mutation was detected in 60% non-neoplastic skin cases (50 % of seborrheic keratosis and 70% of actinic keratosis) and in 73% neoplastic non-melanoma skin cases (100% of BCC and 47% of SCC). Positive staining was detected predominantly in basal cell layer in seborrheic keratosis, and scattered among various layers of epidermis in actinic keratosis. Additionally, positive staining was detected in dermal inflammatory cells and sebaceous glands. Among neoplastic skin lesions, 22/30 cases (73 %) were positive for mutant IDH1 with all 15 cases of BCC (100%) and 7 /15 cases of SCC (47 %). No statistically significant relation between mutant IDH1 and age , gender, number of sites and location of lesions was found. A statistically significant difference between expression of mutant IDH1in BCC and SCC with more intensity of staining among BCC than SCC cases was detected. In BCC patients, the intensity of IDH1 mutant expression (nuclear predominant over cytoplasmic staining) was marked among well differentiated BCC, and lessen among moderately and poorly differentiated BCC. Also, intensity of IDH1 mutant expression in BCC infiltrate was seen till the level of papillary dermis more than the level of reticular dermis. Regarding histopathological variants of BCC, no difference in intensity of staining was observed. In SCC patients, there was no statistically significant relation between mutant IDH1among different depths of infiltration. Although more expression of mutant IDH1 was noticed among well differentiated SCC than poorly differentiated cases, this difference was not statistically significant. Conclusions: IDH1 mutant expression is predominantly detected in basal cells, inflammatory cells and sebaceous glands. IDH1 mutant expression is more in skin lesions with basal cell proliferation (non neoplastic and neoplastic). IDH1 mutant expression among non-melanoma skin cancer (BCC,SCC) is more marked in BCC than SCC. In both BCC & SCC, IDH1 mutant expression decrease with loss of differentiation.
Authors and Affiliations
Sahar F. Mansour, Amal H. A. Gomaa
Keywords
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- EP ID EP244381
- DOI 10.9790/0853-1610097684
- Views 44
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