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Pulmonary adenocarcinoma with signet ring cell features: a comprehensive study from 3 distinct patient cohorts.

ABSTRACT: Comprehensive biological characteristics of pulmonary adenocarcinomas with signet ring cell features (SRC?) are not well known. Herein, we systematically evaluated clinical and molecular features of SRC? cases with particular attention to smoking status. Surgically treated lung adenocarcinomas (n=763) with follow-up ?5 years in 3 cohorts were reviewed: all patients in 2006 to 2007 ("all-comers," n=222; 168 ever-smokers), a never-smoker cohort (n=266), and a cohort of ever-smokers (n=275). SRC? tumors had ?10% of SRCs agreed by 2 pathologists. SRC? cases were tested for rearrangement of ALK and ROS1, as well as 187 known mutations in 10 oncogenes including EGFR, KRAS, BRAF, ERBB2, JAK2, AKT1, AKT2, KIT, MET, and PIK3CA. Overall, 53 of 763 cases (7%) were SRC?. In the 2006 to 2007 "all comer" cohort, 9% were SRC?. In the never-smoker cohort, 9% were SRC?. In the smoker cohort, 3% were SRC?. Univariable analysis showed that SRC? never-smokers had shorter overall and disease-free survival (P=0.006 and 0.0004, respectively), but the significance faded in the multivariable analysis. For the other 2 cohorts, crude 5-year survival was decreased by 6% to 27% in SRC? cases without reaching statistical significance. In SRC? tumors, KRAS mutation was most common (29%), followed by ALK (26%), EGFR (18%), ROS1 (6%), BRAF (6%), and PIK3CA (3%). In summary, SRC? tumors in never-smokers had a worse survival by univariable analysis only. SRC? cases seemed enriched for ALK? and ROS1?, and other mutations were generally in keeping with the patient's smoking status.

SUBMITTER: Boland JM

PROVIDER: S-EPMC4410841 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Pulmonary adenocarcinoma with signet ring cell features: a comprehensive study from 3 distinct patient cohorts.

Boland Jennifer M JM Wampfler Jason A JA Jang Jin S JS Wang Xiaoke X Erickson-Johnson Michele R MR Oliveira Andre M AM Yang Ping P Jen Jin J Yi Eunhee S ES

The American journal of surgical pathology 20141201 12

Comprehensive biological characteristics of pulmonary adenocarcinomas with signet ring cell features (SRC⁺) are not well known. Herein, we systematically evaluated clinical and molecular features of SRC⁺ cases with particular attention to smoking status. Surgically treated lung adenocarcinomas (n=763) with follow-up ≥5 years in 3 cohorts were reviewed: all patients in 2006 to 2007 ("all-comers," n=222; 168 ever-smokers), a never-smoker cohort (n=266), and a cohort of ever-smokers (n=275). SRC⁺ t ...[more]

PMID: 25007143

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Project description:BackgroundWe performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.MethodsBetween 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.ResultsA 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.ConclusionsColorectal 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.

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Pulmonary adenocarcinoma with signet ring cell features: a comprehensive study from 3 distinct patient cohorts.

Publications

Pulmonary adenocarcinoma with signet ring cell features: a comprehensive study from 3 distinct patient cohorts.

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