ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on survival.
BACKGROUND
Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair mechanism. Ki67 is associated with the clinical course of several malignancies. The associations of ERCC1 and Ki67, clinical features and survival in small cell lung carcinoma (SCLC), typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LCNEC) were determined.


METHODS
We included a consecutive series of 186 patients with SCLC treated with platinum-based chemotherapy and surgically treated patients with TC (n = 48), AC (n = 15) and LCNEC (n = 27). ERCC1 and Ki 67 were measured by immunohistochemistry and scored using published criteria.


RESULTS
The expression of ERCC1 was different among the different tumor types (p < 0.001). For patient with limited disease as well as extensive disease SCLC, no association of ERCC1 expression with survival was observed (p = 0.59). However, only 10% of SCLC tumors expressed ERCC1. For TC and AC, ERCC1 positive patients had better survival than ERCC1 negative patients. ERCC1 had no prognostic impact for LCNEC. A difference of the percentage of Ki67 LI was observed for the different tumor types (p < 0.001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC+AC) and high grade NE (LCNEC + SCLC) (p < 0.001). For all included patients, a correlation between Ki67 and ERCC1 was observed (RSquare = 0.19, p < 0.001).


CONCLUSIONS
ERCC1 expression in SCLC treated with platinum-based chemotherapy has no impact on survival. High expression of ERCC1 in TC might represent a clue to the failure of platinum-based therapy in these patients. ERCC1 expression has prognostic impact in lung carcinoids. Ki 67 might be considered as a supplementary test to the histopatologic classification of NE tumors.
Skov
Birgit Guldhammer
BG
Department of Pathology, Gentofte Hospital, DK-2900 Gentofte, Denmark. bigu@heh.regionh.dk
Holm
Bente
B
Erreboe
Anders
A
Skov
Torsten
T
Mellemgaard
Anders
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009944:Organoplatinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases