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Open AccessArticle

Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers

1
National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune, Maharashtra 411007, India
2
Department of Technology, Savitribai Phule Pune University, Pune, Maharashtra 411007, India
3
Department of Pathology, Armed Forces Medical College, Pune, Maharashtra 411040, India
4
Department of Histopathology, Inlaks and Budrani Hospital, Morbai Naraindas Cancer Institute, Koregaon Park, Pune, Maharashtra 411001, India
5
Department of Pathology, KEM Hospital, Pune, Maharashtra 411011, India
6
Department of Oncopathology, Tata Medical Centre, Kolkata, West Bengal 700 156, India
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(3), 330; https://doi.org/10.3390/jcm8030330
Received: 31 January 2019 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 8 March 2019
Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a pertinent approach in improving prognosis of this highly heterogeneous disease. Enabling the same necessitates identification of class-specific biomarkers and their robust detection in the clinic. We have earlier resolved three discrete molecular HGSC classes associated with distinct functional behavior based on their gene expression patterns, biological networks, and pathways. An important difference revealed was that Class 1 is likely to exhibit cooperative cell migration (CCM), Class 2 undergoes epithelial to mesenchymal transition (EMT), while Class 3 is possibly capable of both modes of migration. In the present study, we define clinical stratification of HGSC tumors through the establishment of standard operating procedures for immunohistochemistry and histochemistry based detection of a panel of biomarkers including TCF21, E-cadherin, PARP1, Slug, AnnexinA2, and hyaluronan. Further development and application of scoring guidelines based on expression of this panel in cell line-derived xenografts, commercial tissue microarrays, and patient tumors led to definitive stratification of samples. Biomarker expression was observed to vary significantly between primary and metastatic tumors suggesting class switching during disease progression. Another interesting feature in the study was of enhanced CCM-marker expression in tumors following disease progression and chemotherapy. These stratification principles and the new information thus generated is the first step towards class-specific personalized therapies in the disease. View Full-Text
Keywords: high-grade serous ovarian carcinoma; epithelial-to-mesenchymal transition; molecular stratification; biomarkers; scoring system; immunohistochemistry high-grade serous ovarian carcinoma; epithelial-to-mesenchymal transition; molecular stratification; biomarkers; scoring system; immunohistochemistry
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Kamble, S.C.; Sen, A.; Dhake, R.D.; Joshi, A.N.; Midha, D.; Bapat, S.A. Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers. J. Clin. Med. 2019, 8, 330.

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