TY - JOUR
T1 - Significant Tumor Regression after Neoadjuvant Chemotherapy in Gastric Cancer, but Poor Survival of the Patient? Role of MHC Class I Alterations
AU - Hiltner, Theresa
AU - Szörenyi, Noémi
AU - Kohlruss, Meike
AU - Hapfelmeier, Alexander
AU - Herz, Anna Lina
AU - Slotta-Huspenina, Julia
AU - Jesinghaus, Moritz
AU - Novotny, Alexander
AU - Lange, Sebastian
AU - Ott, Katja
AU - Weichert, Wilko
AU - Keller, Gisela
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
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.
KW - B2M
KW - HLA
KW - adenocarcinoma
KW - allelic imbalance
KW - gastric
KW - gastroesophageal junction
KW - loss of heterozygosity
KW - neoadjuvant chemotherapy
KW - prognosis
KW - tumor regression
UR - http://www.scopus.com/inward/record.url?scp=85147890379&partnerID=8YFLogxK
U2 - 10.3390/cancers15030771
DO - 10.3390/cancers15030771
M3 - Article
AN - SCOPUS:85147890379
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 3
M1 - 771
ER -