title: A subset of small cell lung cancer with low neuroendocrine expression and good prognosis: a comparison study of surgical and inoperable cases with biopsy.
abstract: Patients with small cell lung carcinoma (SCLC) rarely demonstrate long-term survival. We previously reported that gene expression profiling identified a subset of SCLC with good prognosis in surgical cases. To find an easier way to routinely identify SCLC belonging to this subset, we conducted the present study with a hypothesis that neuroendocrine (NE) or basaloid (BA) phenotypes may influence prognosis. To confirm the subset, we used an array platform to analyze fresh samples. Because inoperable cases may differ from surgical cases, we enrolled 51 biopsy cases and 43 resected samples. To evaluate NE and BA phenotypes, we used NE (synaptophysin, chromogranin A, and CD56) and BA (p63 and CK34βE12) markers. To varying extents, expression profiling based on the array platform duplicated the subsets. For NE phenotypes, 77% of surgical cases and 100% of biopsy cases were positive for at least 1 marker. For BA phenotypes, only 19% of surgical cases were positive for at least 1 marker, whereas there were no positive biopsy cases. Cases undergoing surgery were categorized based on NE and BA immunoreactivity; 58% into NE+BA-, 19% into NE+BA+, 23% into NE-BA-, and 0 into NE-BA+ groups. NE- patients (n = 10) demonstrated a significantly better prognosis (P = .0306) than their NE+ counterparts (n = 33), whereas no survival difference was evident between the BA+ and BA- groups. Multivariate analyses showed that NE positivity was an independent prognostic factor. In conclusion, the SCLC subset with good prognosis is identified by low NE marker expression, which was found only in surgical cases.
authors.affiliation: Division of Pathology, The Cancer Institute, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan; Department of Thoracic Surgery, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Hamanaka
authors.affiliation: Division of Pathology, The Cancer Institute, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-0041, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Genome Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ushijima
authors.affiliation: Division of Pathology, The Cancer Institute, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Division of Pathology, The Cancer Institute, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hatano
authors.affiliation: Division of Respiratory Surgery, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uehara
authors.affiliation: Division of Respiratory Surgery, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.affiliation: Division of Respiratory Surgery, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Division of Respiratory Medicine, Thoracic Oncology Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
authors.affiliation: Division of Respiratory Medicine, Thoracic Oncology Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horai
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-0041, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Genome Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.affiliation: Department of Thoracic Surgery, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwasaki
authors.affiliation: Division of Pathology, The Cancer Institute, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan. Electronic address: ishikawa@jfcr.or.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D019002:CD56 Antigen / Q000032:analysis; D018278:Carcinoma, Neuroendocrine / Q000473:pathology; D053379:Chromogranin A / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000401:mortality; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis; D055752:Small Cell Lung Carcinoma / Q000737:chemistry* / Q000473:pathology / Q000601:surgery*; D016708:Synaptophysin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019002:CD56 Antigen; C081876:CKAP4 protein, human; D053379:Chromogranin A; D008565:Membrane Proteins; C522918:NCAM1 protein, human; D016708:Synaptophysin; D007633:Keratins
keywords: Basal cell; Immunohistochemistry; Neuroendocrine; Prognosis; Small cell lung cancer (SCLC)