Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung.
OBJECTIVE
Recently, several matrix metalloproteinases (MMPs) have shown promise as prognosticators in non-small cell lung cancer. In this study, we sought to validate the importance of MMP-9 and to study the relationships between MMP-9 and several other tumor or stromal markers.


METHODS
We examined MMP-9 and several other markers in tumor tissues from 152 patients with surgically excised adenocarcinomas of the lung. Their preoperative clinical stages were T(1-4)N(0)M(0); however, pathological exam of their resected tissues demonstrated that 33 were stage II, and 64 were stage III. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for MMP-9, and the outcome for our study was survival time until death from recurrent lung cancer.


RESULTS
Multivariate Cox model analysis demonstrated that pathological stage was significantly related to survival time (P < 0.01), but quantitative staining of the tumor for MMP-9 added prognostic information (P < 3.0 x10(-16)) and was more strongly prognostic than pathological stage. In the subset of pathological stage I patients, staining for MMP-9 was also significantly associated with survival (P < 1.0 x10(-6)), and a cutpoint at the median staining of 11.2% for MMP-9 divided them into two groups with distinctive survival times. Those with MMP-9 > 11.2% had a median survival time of just 11 months. Those with MMP-9 < 11.2% had not reached a median survival and had a mean survival time of >62 months.


CONCLUSIONS
Tumor staining for MMP-9 in resected adenocarcinoma of the lung is strongly related to survival. Patients with >11.2% staining in their tumors comprise a subset with a high hazard for dying of lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.
Pinto
Clovis Antônio
CA
Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
Carvalho
Paulo Eduardo de Oliveira
PE
Antonângelo
Leila
L
Garippo
Ana
A
Da Silva
Alecsander Guillaumon Pereira
AG
Soares
Fernando
F
Younes
Riad
R
Beyruti
Ricardo
R
Takagaki
Teresa
T
Saldiva
Paulo
P
Vollmer
Robin T
RT
Capelozzi
Vera Luiza
VL
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D020780:Matrix Metalloproteinase 9