PMID- 25963795
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20181113
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Linking)
VI  - 141
IP  - 12
DP  - 2015 Dec
TI  - Clinicopathological significance of cancer stem-like cell markers in high-grade 
      neuroendocrine carcinoma of the lung.
PG  - 2121-30
LID - 10.1007/s00432-015-1985-3 [doi]
AB  - PURPOSE: This study aimed to evaluate the clinicopathological significance of 
      cancer stem-like cell (CSLC) markers in high-grade neuroendocrine carcinoma 
      (HGNEC) of the lung, including small cell lung carcinoma (SCLC) and large cell 
      neuroendocrine carcinoma (LCNEC). METHODS: We retrospectively studied patients 
      who underwent surgical resection of SCLC (n = 60) and LCNEC (n = 45) to analyze 
      their clinicopathological profiles and the immunohistochemical expression of 
      putative CSLC markers (Caveolin, Notch, CD44, CD166, SOX2, ALDH1, and Musashi1). 
      Staining scores for these markers in tumor cells were calculated by multiplying 
      the percentage of positive tumor cells per lesion by the staining intensity level 
      (0, 1, and 2); a score of >/= 10 represented positive expression. RESULTS: There 
      was a difference between SCLC and LCNEC with respect to both SOX2 (55 vs. 27 %, p 
      = 0.003) and CD166 (27 vs. 47 %, p = 0.034) expression. ALDH1 expression was 
      equally observed in SCLC and LCNEC (67 vs. 73 %, p = 0.46), and patients with 
      ALDH1-positive HGNEC had significantly worse recurrence-free survival (RFS) and 
      overall survival (OS) rates than those with ALDH1-negative HGNEC (5-year RFS: 39 
      vs. 67 %, p = 0.009; 5-year OS: 50 vs. 79 %, p = 0.021). A multivariate analysis 
      revealed that positive ALDH1 expression was an independent unfavorable prognostic 
      factor with respect to both RFS and OS. CONCLUSIONS: The differences in the 
      expression profiles of CSLC markers might reflect morphological differences 
      between SCLC and LCNEC. Positive ALDH1 expression in lung HGNEC was associated 
      with an unfavorable patient prognosis, which suggested that ALDH1-positive tumor 
      cells might be future therapeutic targets for the treatment of lung HGNEC.
FAU - Morise, Masahiro
AU  - Morise M
AD  - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, 
      Japan.
AD  - Pathology Division, Research Center for Innovative Oncology, National Cancer 
      Center Hospital East, Kashiwa, Japan.
FAU - Hishida, Tomoyuki
AU  - Hishida T
AD  - Department of Thoracic Surgery, National Cancer Center Hospital East, 6-5-1, 
      Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. thishida@east.ncc.go.jp.
FAU - Takahashi, Akiko
AU  - Takahashi A
AD  - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, 
      Japan.
FAU - Yoshida, Junji
AU  - Yoshida J
AD  - Department of Thoracic Surgery, National Cancer Center Hospital East, 6-5-1, 
      Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
FAU - Ohe, Yuichiro
AU  - Ohe Y
AD  - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, 
      Japan.
AD  - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Nagai, Kanji
AU  - Nagai K
AD  - Department of Thoracic Surgery, National Cancer Center Hospital East, 6-5-1, 
      Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
FAU - Ishii, Genichiro
AU  - Ishii G
AD  - Pathology Division, Research Center for Innovative Oncology, National Cancer 
      Center Hospital East, Kashiwa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150512
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*metabolism
MH  - Carcinoma, Large Cell/metabolism/mortality/*secondary
MH  - Carcinoma, Neuroendocrine/metabolism/mortality/*secondary
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lung Neoplasms/metabolism/mortality/*pathology
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Invasiveness
MH  - Neoplasm Recurrence, Local/metabolism/mortality/*pathology
MH  - Neoplasm Staging
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - Prognosis
MH  - Retrospective Studies
MH  - Small Cell Lung Carcinoma/metabolism/mortality/*secondary
MH  - Survival Rate
MH  - Young Adult
OTO - NOTNLM
OT  - Aldehyde dehydrogenase 1 (ALDH1)
OT  - Cancer stem-like cells
OT  - High-grade neuroendocrine carcinoma
OT  - Large cell neuroendocrine carcinoma
OT  - Small cell lung carcinoma
EDAT- 2015/05/13 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/05/13 06:00
PHST- 2015/01/18 00:00 [received]
PHST- 2015/04/28 00:00 [accepted]
PHST- 2015/05/13 06:00 [entrez]
PHST- 2015/05/13 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1007/s00432-015-1985-3 [pii]
AID - 10.1007/s00432-015-1985-3 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2015 Dec;141(12):2121-30. doi: 
      10.1007/s00432-015-1985-3. Epub 2015 May 12.