Pre neoplastic lesions Peroxisome proliferator activated receptor (PPARϒ) in precancerous lesions : panoramic emerging insights Author : Dr Geethanjali Bhas MBBS,MD ,DNB, Membership Associate Royal College of Pathologists (UK) Associate professor of Pathology International Medical School, MSU INTRODUCTION Peroxisome proliferator activated receptorϒ (PPAR ϒ) is a nuclear hormonal receptor with protean cellular functions in proliferation, differentiation and apoptosis. It is also involved in several carcinogenetic pathways. PPAR ϒ is variably and differentially expressed in various pre neoplastic lesions with associated ligand modulated responses. Despite numerous current and future implications in terms of preventive and therapeutic modulatory strategies, the realm of PPAR ϒ in precancerous lesions is underexplored. This study therefore, encapsulates the key emerging insights on PPAR ϒ expression in precancerous lesions of breast, colon , esophagus, cervix, larynx, endometrium and skin. Key words : 3 Gastric precancerous lesions : PPAR ϒ expression was significantly higher in intestinal metaplasia and adenoma, Nuclear expression was higher in adenoma. Normal gastric mucosa showed no physiological expression and activity Cervix : Significantly higher expression of PPAR ϒ (P< 0.05) in CIN as compared to normal cervical tissue but lower than in cervical cancer. Prostate : Significant PPAR ϒ expression was found in prostatic intraepithelial neoplasia (PIN). Weak or no PPAR expression was found in Benign prostatic hyperplasia. Barrett esophagus : Significantly higher expression of PPAR ϒ and m RNA expression in Barret's involved epithelium as compared to normal uninvolved epithelium. However, increasing levels of PPAR ϒ expression was observed with decreasing levels of differentiation Endometrium: PPAR ϒ expression was significantly higher in endometrial hyperplasia as compared to normal and cancerous endometrium. : PPAR ϒ was also expressed in normal endometrium Colon: Murine models showed that : PPAR ϒ expression was found in a subset of adenomas and carcinomas .It was not expressed in normal epithelium. Skin : PPAR ϒ was comparable in normal, actinic keratosis, SCC Breast : , PPARγ expression remained negatively associated with recurrence, with an OR of 0.17 . This study suggests that presence of PPARγ in DCIS may be protective against ipsilateral recurrence particularly in Grade 2 and 3 lesions. Overall, PPAR ϒ was found to have a protective effect against cancers of colon, stomach and endometrium whereas in the oesophagus it has been found to promote carcinogenesis. Peroxisome proliferator activated receptor gamma (: PPAR ϒ ) is found to be actively expressed in precancerous lesions of breast, stomach, cervix, skin, prostate, esophagus, endometrium and colon. Precancerous lesions of stomach, cervix, prostate, endometrium and colon show increased PPAR ϒ expression as compared to normal epithelium and invasive cancer. Exceptionally , esophageal cancer shows increased PPAR ϒ as compared to precancerous lesions. Increasing levels of PPAR gamma expression was observed with decreasing levels of differentiation PPAR ϒ expression in precancerous skin lesions as compared to invasive cancer was equivocal. Regarding breast Ductal carcinoma in situ: PPAR ϒ expression suggests a protective effect in ipsilateral recurrence. Overall, PPAR ϒ was found to have a protective effect against cancers of colon, stomach and endometrium whereas in the oesophagus it has been found to promote carcinogenesis This study highlights the significance of assessing PPARγ in pre neoplastic lesions and focuses areas where further research is needed to explore the clinicopathological significance and therapeutic utility of variable expressivity . PPAR ϒ Pre neoplastic lesions Expression patterns of PPAR ϒ in adenoma colon, gastric intestinal metaplasia and dysplasia, Barret esophagus, prostatic intra epithelial neoplasia, CIN cervix, endometrial hyperplasia, non melanocytic precursors of skin cancer Comparing PPAR ϒ expression patterns in normal , precancerous lesions and invasive cancers Elucidating recurrence risk in PPAR gamma expressing pre neoplastic lesions PPAR Pre cancerous Normal PPAR expression PPAR expression is enhanced in precancerous lesions of colon, stomach, cervix, colon when compared to normal epithelium COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ Swati Kulkarni, Deepa B Patil, [...], and Seema A KhanBMC cancer Expression of PPARγ, p27 and Ki67 in Cervical Cancer and Clinical SignificanceJ Int Transl Med, 2015, 3(1):11-17 Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancerYoshihiro Segawa1 Hajime Sano2The ProstateVolume 51, Issue 2, pages 108–116, 1 May 2002 Peroxisome proliferator-activated receptor expression and activation in normal human colonic epithelial cells and tubular adenomas2005, Vol. 40, No. 2 J Exp Clin Cancer Res. 2006 Sep;25(3):443-8. Differential expression of peroxisome proliferator-activated receptor in histologically different human gastric cancer tissues Oncol Res. 2011;19(3-4):141-7. Enhanced PPAR-gamma expression may correlate with the development of Barrett's esophagus and esophageal adenocarcinoma. Wang W et al Peroxisome Proliferator-Activated Receptor and Growth Inhibition by Its Ligands in Uterine Endometrial Carcinoma Kyoko Ota An extensive literature search of the Medline , Embase and PubMed databases were explored using the key words PPAR ϒ , peroxisome proliferator activated receptor gamma, pre neoplastic lesions, PPAR ϒ expression, CIN, carcinoma in situ, dysplasia, adenoma colon, Prostatic intra epithelial neoplasia, Barret esophagus, gastric intestinal dysplasia, precancerous skin lesions, endometrial hyperplasia and PPAR ϒ ligands and activation, carcinogenesis. A descriptive method has been adopted in this study to gain insight on the various patterns of PPAR gamma expression in pre neoplastic lesions. Studies involving therapeutic outcomes have been excluded as this is beyond the current scope of this poster presentation cancer Pre cancerous PPAR PPAR ϒ expression is precancerous lesions is higher when compared to invasive cancer . Exceptions are esophageal cancers where PPAR GAMMA EXPRESSION is higher than in pre cancers.