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J Thorac Cardiovasc Surg. 2006 May;131(5):1014-20.

Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: an analysis of 5018 hospital- and 712 population-based cases.

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Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.



Our objective was to determine whether histologic grade independently contributes to the prognosis of non-small cell lung cancer.


A total of 5018 hospital-based patients diagnosed from 1997 to 2003 and 712 population-based patients diagnosed from 1984 to 2003 were followed up through the end of 2004. The effect of histologic grade on postdiagnosis survival or postresection recurrence was evaluated by Cox proportional hazards models. Relative risks (RR) were estimated by comparing undifferentiated, poorly differentiated, and moderately differentiated carcinoma with well-differentiated carcinoma.


Histologic grade was significantly associated with survival after adjustment for the effects of age, gender, smoking history, tumor stage, histologic cell type, and treatment modality. Patients with undifferentiated carcinoma had an 80% elevated risk of death (RR = 1.83; 95% confidence interval [CI], 1.4-2.4) compared with those with well-differentiated carcinoma; 70% and 40% elevated risks were observed for patients with poorly and moderately differentiated carcinoma, respectively (RR, 1.7 [1.5-2.0] and 1.4 [1.2-1.6]). Similar results were observed for 718 incidence cases in which the relative risks were 1.6 (1.1-2.2) and 1.4 (1.0-1.9) for poorly/undifferentiated carcinoma and moderately differentiated carcinoma, respectively. Patients with less-differentiated carcinoma after tumor resection had a higher risk of recurrence, with adjusted hazard ratios of 2.1 (95% CI: 1.4-2.9) and 1.4 (1.0-1.9) for poorly/undifferentiated and moderately differentiated carcinoma compared with well-differentiated carcinoma.


Histologic grade has significant prognostic value for survival of patients with non-small cell lung cancer. Histologic grade may provide useful information in defining the aggressiveness of tumors and should be considered as an independent factor affecting survival beyond TNM staging.

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