title: The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC).
abstract: We evaluated whether ribonucleotide reductase regulatory subunit M1 (RRM1) protein expression by immunohistochemistry (IHC) is a predictor of survival and response in gemcitabine-treated, advanced non-small cell lung cancer (NSCLC). We retrospectively collected 40 formalin-fixed, paraffin-embedded NSCLC tissues to investigate the protein expression of RRM1 by IHC with a purified rabbit anti-human RRM1 polyclonal antibody (ProteinTech Group, Chicago, IL, USA). RRM1 expression was positive in 14 (35%) and negative in 26 (65%) cases. Ten (25%) patients were treated as first-line and 30 (75%) patients as second-line. The median age was 61 years and M/F was 31/9. Stage IIIB/IV was 7/33 and adenocarcinoma/squamous cell carcinoma/other cell type was 20/16/4. Other characteristics, including age, gender, stage, cell type and first/second-line were not statistically different in the RRM-positive and RRM-negative groups. The overall survival of RRM1-positive groups was significantly shorter than RRM-negative groups (5.1 months vs. 12.9 months, p = 0.022). The response rates of 38 out of 40 patients were assessable. Disease control rate (PR+SD) of the RRM1-positive groups was significantly lower than that of RRM1-negative groups (23% vs. 56%, p = 0.053). In patients with gemcitabine-treated advanced NSCLC, patients with RRM1-positive tumors had worse overall survival and disease control than patients with RRM1-negative tumors.
authors.affiliation: Department of Medical Oncology & Hematology, East-West Neo Medical Center, Kyung Hee University, #149 Sangil-dong, Gangdong-gu 134-727 Seoul, Republic of Korea. lj2lj2@hanmail.net
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Maeng
authors.forename: Seon Kyung
authors.initials: SK
authors.lastname: Baek
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Jee-Hong
authors.initials: JH
authors.lastname: Yoo
authors.forename: Cheon Woong
authors.initials: CW
authors.lastname: Choi
authors.forename: Yee Hyung
authors.initials: YH
authors.lastname: Kim
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Kwak
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Jung Bo
authors.initials: JB
authors.lastname: Kim
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase