Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer

Cancers

Thomas Schmidt¹  Katja Ott²  Alexander Novotny³  Alexander Hapfelmeier⁴  Moritz Jesinghaus⁵  Gisela Keller⁵  Julia Slotta-Huspenina⁵  Katja Steiger⁵  Bianca Grosser⁵  Nicole Pfarr⁵  Meike Kohlruss⁵  Wilko Weichert⁵  MatthiasM. Gaida⁶ 

[1]Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany

[2]Department of Surgery, Klinikum Rosenheim, 83022 Rosenheim, Germany

[3]Department of Surgery, TUM School of Medicine, Technical University of Munich, 81675 Munich, Germany

[4]Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich, 81675 Munich, Germany

[5]Institute of Pathology, TUM School of Medicine, Technical University of Munich, 81675 Munich, Germany

[6]Institute of Pathology, University of Heidelberg, 69120 Heidelberg, Germany

关键词: p53;    adenocarcinoma;    gastric;    gastroesophageal junction;    prognosis;    neoadjuvant chemotherapy;   

DOI  :  10.3390/cancers12061689

来源: DOAJ

【 摘 要 】

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI‑H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.

【 授权许可】

Unknown