Meeting
2023 ASCO Gastrointestinal Cancers Symposium
Immunohistochemistry-based molecular classification of gastric cancer in India: How are we different?
Authors
Biswajit Dubashi
Jawaharlal Institute of Post-Graduate Medical Education and Research, Puducherry, India;
Biswajit Dubashi , Charles L , Yadav Nisha , Rajesh Nachiappa Ganesh , Vikram Kate , Prasanth Penumadu , Sandhiya Selvarajan , Kalayarasan Raja , Smita Kayal , Prasanth Ganesan
Organizations
Jawaharlal Institute of Post-Graduate Medical Education and Research, Puducherry, India; , JIPMER, Puducherry, India; , Jawaharlal Institute of Post-Graduate Medical Education and Research Jipmer, Puducherry, India; , Department of Medical Oncology, Regional Cancer Centre, Dhanavantri Nagar, JIPMER, Puducherry, India;
Research Funding
Other
Jawaharlal Institute of Postgraduate Medical Education & Research
Background: TCGA and ACRG have classified gastric cancer (GC) into molecular subgroups using genomics. We attempted to classify GC from our region using IHC (Immunohistochemistry) to understand its prognostic significance and compare with similar data from other parts of the world. Methods: This was a retrospective cohort of GC patients from years 2017-18. EBV (LMP), MSI (MLH1, MSH2, PMS2, MSH6),p53, E-cadherin and PIK3CA were assessed by IHC. Clinicopathological characteristics and survival were evaluated for association with molecular subtypes as defined by TCGA and ACRG classification system. Results: A total of 191patients were included with EBV positivity 35 (18.3 %), MSI 33(17.3 %), p-53 aberration 25(13.1%), E-cadherin negative (29.3%). On univariate analysis, p53 aberration was associated with higher age (>60 yrs), E- cadherin negative with diffuse histology & antro-pyloric region as predominant site. MSI with intestinal histology & antro-pyloric region as predominant site with MSI. The TCGA classification revealed EBV 35 (18%), MSI 28 (15 % ), GS 48 (25 %) and CIN 80 (42% ) subtypes respectively. CIN subtype was seen predominantly above 40 yrs of age (P=0.04), GS subtype was frequently associated with diffuse histology P<0.0001. The ACRG classification revealed MSI 33(17%), MSS/EMT 51 (26.7%), MSS/ p53 normal 91 (47.6%) and MSS/p53 aberrant 16 (8.4) subtypes. MSS/E-cad- subtype was associated with diffuse histology. PIK3CA positivity was higher in CIN (TCGA )& MSI (dmr) (ACRG) respectively. The median OS in MSI was 35 and 32 months higher compared to other subtypes (P<0.0001) in TCGA and ACRG classification respectively. Conclusions: The TCGA and ACRG classification identified molecular subtypes based on IHC from our region and significantly correlated with clinical factors and survival. PIK3CA as an additional marker may be further explored to be included in the classification system. Abbreviation: EBV - Epstein–Barr-virus, MSI – Microsatellite-Instability, GS- Genomic-instability, CIN- Chromosomal-instability, MSS- Microsatellite-stable, EMT-Epithelial-mesenchymal-transition.
Sl.No | Variable | TCGA | ACRG | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N (%) |
I (EBV)
N=35 (18.3) |
II (MSI)
N=28 (14.7) |
III (CIN)
N=80 (41.9) |
IV(GS)
N=48 (25.1) | P-Value |
I (MSI)
N=33 (17.3) |
II
(MSS/EMT) N=51 (26.7) |
III
(MSS/p53 aberrant) N=16 (8.4) |
IV
(MSS/p Normal) N=91 (47.6) | P-Value | ||
| 1 | Age (n=191) | ≤40 | 10 (28.6) | 3(10.7) | 8(10.0) | 5(10.4) | 0.04 | 5(15.2) | 6(11.8) | 0(0.0) | 15(16.5) | 0.352 |
| >40 | 25(71.4) | 25(89.3) | 72(90.0) | 43(89.6) | 28(84.8) | 45(88.2) | 16(100.0) | 76(83.5) | ||||
| 2 | Histology (n=189) | Diffuse | 10 (28.6) | 7(25.0) | 22(27.8) | 36(76.6) | <0.0001 | 7 (21.2) | 37(74.0) | 2 (13.3) | 29(31.9) | <0.0001 |
| Intestinal | 25(71.4) | 51(75.0) | 57(72.2) | 11(23.4) | 26 (78.8) | 13(26.0) | 13(86.7) | 62(68.1) | ||||
| 3 | PIK3CA (n=191) | Positive | 14(23.3) | 12(20.0) | 27(45.0) | 7(11.7) | 0.02 | ) 14(23.3) | 7(11.7) | 5(8.3) | 34(56.7) | 0.013 |
| 4 | Survival (n=191) | OS (months) | 16 (9.4- 22.6) | 35 (28.3- 41.7) | 9(6.5- 11.5) | 9(6.2- 11.8) | <0.0001 | 32(17.4-46.6) | 9(6.4-11.6) | 9(1.2-16.8) | 9 (5.8-12.2) | <0.0001 |
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session A: Cancers of the Esophagus and Stomach and Other GI Cancers
Track
Esophageal and Gastric Cancer,Other GI Cancer
Sub Track
Tumor Biology, Biomarkers, and Pathology
Citation
J Clin Oncol 41, 2023 (suppl 4; abstr 462)
DOI
10.1200/JCO.2023.41.4_suppl.462
Abstract #
462
Poster Bd #
L8
Abstract Disclosures
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