PMID- 36765729
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230213
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Jan 26
TI  - Significant Tumor Regression after Neoadjuvant Chemotherapy in Gastric Cancer, 
      but Poor Survival of the Patient? Role of MHC Class I Alterations.
LID - 10.3390/cancers15030771 [doi]
LID - 771
AB  - We aimed to determine the clinical and prognostic relevance of allelic imbalance 
      (AI) of the major histocompatibility complex (MHC) class I genes, encompassing 
      the human leukocyte antigen (HLA) class I and beta-2 microglobulin (B2M) genes, 
      in the context of neoadjuvant platinum/fluoropyrimidine chemotherapy (CTx). 
      Biopsies before CTx were studied in 158 patients with adenocarcinoma of the 
      stomach or gastroesophageal junction. The response was histopathologically 
      evaluated. AI was detected by multiplex PCRs analysis of four or five 
      microsatellite markers in HLA and B2M regions, respectively. AI with no marker 
      was significantly associated with response or survival. However, subgroup 
      analysis revealed differences. AI at marker D6S265, close to the HLA-A gene, was 
      associated with an obvious increased risk in responding (HR, 3.62; 95% CI, 
      0.96-13.68, p = 0.058) but not in non-responding patients (HR, 0.92; 95% CI, 
      0.51-1.65, p = 0.773). Markers D6S273 and D6S2872 showed similar results. The 
      interaction between AI at D6S265 and response to CTx was significant in a 
      multivariable analysis (p = 0.010). No associations were observed for B2M 
      markers. Our results underline the importance of intact neoantigen presentation 
      specifically for responding patients and may help explain an unexpectedly poor 
      survival of a patient despite significant tumor regression after neoadjuvant 
      platinum/fluoropyrimidine CTx.
FAU - Hiltner, Theresa
AU  - Hiltner T
AUID- ORCID: 0000-0001-7933-0966
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
FAU - Szorenyi, Noemi
AU  - Szorenyi N
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
FAU - Kohlruss, Meike
AU  - Kohlruss M
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
FAU - Hapfelmeier, Alexander
AU  - Hapfelmeier A
AD  - Institute of Medical Informatics, Statistics and Epidemiology, Technical 
      University of Munich, 81675 Munich, Germany.
AD  - Institute of General Practice and Health Services Research, School of Medicine, 
      Technical University of Munich, 81675 Munich, Germany.
FAU - Herz, Anna-Lina
AU  - Herz AL
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
FAU - Slotta-Huspenina, Julia
AU  - Slotta-Huspenina J
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
FAU - Jesinghaus, Moritz
AU  - Jesinghaus M
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
AD  - Institute of Pathology, University Hospital Marburg, 35043 Marburg, Germany.
FAU - Novotny, Alexander
AU  - Novotny A
AUID- ORCID: 0000-0002-8029-5958
AD  - Department of Surgery, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
FAU - Lange, Sebastian
AU  - Lange S
AD  - II. Medizinische Klinik, Klinikum rechts der Isar, Technical University of 
      Munich, 81675 Munich, Germany.
FAU - Ott, Katja
AU  - Ott K
AD  - Department of Surgery, Klinikum Rosenheim, 83022 Rosenheim, Germany.
FAU - Weichert, Wilko
AU  - Weichert W
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Munich, Institute of Pathology, 
      81675 Munich, Germany.
FAU - Keller, Gisela
AU  - Keller G
AUID- ORCID: 0000-0003-2886-0371
AD  - Institute of Pathology, TUM School of Medicine, Technical University of Munich, 
      81675 Munich, Germany.
LA  - eng
GR  - 70112177/German Cancer Aid/
GR  - 2019.156.1/Wilhelm-Sander-Stiftung/
PT  - Journal Article
DEP - 20230126
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9913563
OTO - NOTNLM
OT  - B2M
OT  - HLA
OT  - adenocarcinoma
OT  - allelic imbalance
OT  - gastric
OT  - gastroesophageal junction
OT  - loss of heterozygosity
OT  - neoadjuvant chemotherapy
OT  - prognosis
OT  - tumor regression
COIS- W.W. has attended the advisory boards and served as a speaker for Roche, MSD, 
      BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, 
      Amgen, Astellas, Eisai, Johnson & Johnson, Janssen, Illumina, Siemens, Agilent, 
      ADC, GSK, and Molecular Health. W.W. receives research funding from Roche, MSD, 
      BMS, and AstraZeneca. The other authors declare no conflicts of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/12 06:01
PMCR- 2023/01/26
CRDT- 2023/02/11 01:03
PHST- 2022/11/22 00:00 [received]
PHST- 2023/01/17 00:00 [revised]
PHST- 2023/01/20 00:00 [accepted]
PHST- 2023/02/11 01:03 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/12 06:01 [medline]
PHST- 2023/01/26 00:00 [pmc-release]
AID - cancers15030771 [pii]
AID - cancers-15-00771 [pii]
AID - 10.3390/cancers15030771 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Jan 26;15(3):771. doi: 10.3390/cancers15030771.