The prognostic value and pathobiological significance of Glasgow microenvironment score in gastric cancer.
OBJECTIVE
To evaluate the prognostic value and pathobiological significance of Glasgow microenvironment score (GMS), a parameter based on tumor stroma percentage and inflammatory cell infiltration, in gastric cancer.


METHODS
A total of 225 cases of gastric cancer were histologically reviewed, and GMS was evaluated for each case. The association between GMS and patients' survival was investigated. Then the relationship between GMS and mismatch repair (MMR) status, Epstein-Barr virus (EBV) infection were determined using immunohistochemistry (IHC) and in situ hybridization, and the expression of PD1/PD-L1 was examined. Furthermore, the amount of cancer-associated fibroblasts (CAFs), the content and maturity of collagen components were detected using IHC, Picrosirius Red staining and second harmonic generation imaging.


RESULTS
GMS was significantly associated with clinical outcomes of gastric cancer, and multivariate analysis indicated that GMS was an independent factor (HR 1.725, P = 0.002). Low GMS was a manifestation of better prognosis and inflammatory tumor microenvironment, which was related to MMR deficiency (P = 0.042) and EBV infection (P = 0.032), and within this microenvironment, expression of PD-L1 in carcinoma cells (P = 0.030) or in inflammatory cells (P = 0.029) was significantly higher. In contrast, high GMS linked to a poorer survival and desmoplastic stroma, in which there existed markedly increased CAFs and collagen deposition.


CONCLUSIONS
GMS can serve as a useful prognostic factor for gastric cancer, and according to GMS, the tumor microenvironment in this cancer type may be partially classified as inflammatory or desmoplastic microenvironment that possesses different pathobiological features.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China.|Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.|Department of Pathology, The 101 Hospital of People's Liberation Army, Wuxi, Jiangsu Province, China.
Zhi-Hua
ZH
Zhou
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China.|Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
Cheng-Dong
CD
Ji
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China.
Jiang
J
Zhu
Department of Pathology, Daping Hospital, Third Military Medical University, Chongqing, China.
Hua-Liang
HL
Xiao
Department of Pathology, The 101 Hospital of People's Liberation Army, Wuxi, Jiangsu Province, China.
Hai-Bin
HB
Zhao
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China.|Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
You-Hong
YH
Cui
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China. bianxiuwu@263.net.|Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China. bianxiuwu@263.net.
Xiu-Wu
XW
Bian
D060890:B7-H1 Antigen / Q000096:biosynthesis; D020137:Base Pair Mismatch; D003094:Collagen / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D003094:Collagen
Gastric cancer; Glasgow microenvironment score; Prognosis; Tumor microenvironment