Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component.
BACKGROUND
We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.


METHODS
Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.


RESULTS
A slight male predominance was detected in these patients (59.0%). Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54) cases with KRAS mutations in 16.7% (9/54) cases and Nras mutations in 5.4%(3/54) cases. BRAF V600E mutation was detected in 3.7% (2/54) cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9%) cases were composed of ≥50% signet-ring cells; 22 (36.1%) cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.


CONCLUSIONS
Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of signet-ring cells, regardless of the extent, shared similar clinicopathological characteristics, molecular alterations and genetic profiles.
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Qing
Q
Wei
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Xicheng
X
Wang
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Jing
J
Gao
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Jian
J
Li
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Jie
J
Li
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Changsong
C
Qi
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Yanyan
Y
Li
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Zhongwu
Z
Li
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Lin
L
Shen
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000473:pathology*; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012007:Rectum / Q000473:pathology*; D012189:Retrospective Studies
C117307:KRAS protein, human; D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)