Receptor for hyaluronic acid-mediated motility (RHAMM, CD168) expression is prognostically important in both nodal negative and nodal positive large cell lung cancer.
OBJECTIVE
Despite advances in therapy, lung cancer is still the leading cause of cancer-related mortality in the world. Further prognostic tools are warranted for risk-adapted therapeutic decisions. We analysed a cohort of primary surgically treated non-small cell lung cancers (NSCLCs) to determine the prognostic role of CD44 and associated molecules (receptor for hyaluronic acid-mediated motility (RHAMM), CD95, osteopontin (OPN), P-glycoprotein (P-gp) and caspase 3 (Casp3)). CD44 is a cell adhesion molecule. While the standard form (CD44s) is ubiquitously expressed, its variant isoforms are claimed to play an important role in invasion and metastasis in various cancers.


METHODS
Three-hundred and eighty-three primary surgically resected NSCLC specimens were brought into a standardised tissue microarray platform. Immunohistochemistry for CD44, CD95, RHAMM, OPN, P-gp and Casp3 was performed. The clinical correlation was made with known histopathological, phenotypical and genotypical variables; clinical data were available for a postoperative follow-up period of up to 15 years.


RESULTS
RHAMM expression in the subgroup of large cell carcinomas (LCC) was associated with inferior survival (p=0.000223). Median overall survival was 92 versus 18 months for RHAMM-negative and positive patients, respectively. This survival difference remained significant in both nodal negative and positive patients (pN0: p=0.013 and pN≥1: p=0.007, respectively). P-gp expression was associated with inferior survival in adenocarcinomas (ACA; p=0.013) and appeared to be a postsurgical Union International Contre le Cancer (pUICC)- stage and gender-independent prognostic factor, irrespective of adjuvant chemotherapy, in the multivariable analysis; considering nodal status, this survival difference applied to pN0 cancers (p=0.026).


CONCLUSIONS
Analysis of RHAMM expression is a valuable predictor of survival in LCC. RHAMM-positive patients may benefit from a targeted therapy even in early nodal negative stages. Expression of P-gp identifies a subset of pN0 ACA patients with poor outcome independent of stage, gender and adjuvant chemotherapy.
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria Department of Pathology, University Hospital Basel, Basel, Switzerland.
Florian
F
Augustin
Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Michael
M
Fiegl
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Thomas
T
Schmid
Department of Pathology, University Hospital Basel, Basel, Switzerland.
Geoffrey
G
Pomme
Institute of Pathology, Bayreuth, Germany.
William
W
Sterlacci
Department of Pathology, University Hospital Basel, Basel, Switzerland.
Alexandar
A
Tzankov
D000230:Adenocarcinoma / Q000276:immunology* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018287:Carcinoma, Large Cell / Q000276:immunology* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D016009:Chi-Square Distribution; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor
CELL ADHESION MOLECULES; IMMUNOHISTOCHEMISTRY; LUNG CANCER