Detection of micrometastases in pN0 non-small cell lung cancer: an alternative method combining tissue microarray and immunohistochemistry.
OBJECTIVE
To present an alternative method of detecting micrometastases in lymph nodes previously testing negative for non-small cell lung cancer (NSCLC) by routine hematoxylin-eosin staining.


METHODS
A total of 77 hilar and mediastinal lymph nodes resected from 18 patients with NSCLC were investigated for the presence of micrometastases using a combination of microarray analysis and immunohistochemistry.


RESULTS
Micrometastases were detected by identifying cytokeratin- and chromogranin-positive cells in lymph node microarrays. Of the 18 patients initially staged as pN0 through routine hematoxylin-eosin staining, 9 (50%) were restaged as N1, and the prognoses were re-evaluated in terms of histological and clinical parameters. The comparison of the survival curves revealed that survival was higher in the patients without micrometastases than in those with micrometastases. In addition, in the multivariate analysis adjusted for age, gender, histological type, and restaging, the presence of micrometastases proved to be an independent predictor of survival. Among patients who had been previously staged as pN0, the risk of death was found to be 7-times greater for those later diagnosed with micrometastases than for those in whom no micrometastases were identified.


CONCLUSIONS
The combination of microarray analysis and immunohistochemistry might represent a low-cost and less time-consuming alternative for identifying occult micrometastases and predicting prognoses in surgically resected patients with pN0 NSCLC. Larger randomized, prospective studies are needed in order to determine the accuracy of this method.
Franco
Maíra Rovigatti
MR
University of São Paulo School of Medicine - São Paulo, Brazil.
Parra
Edwin Roger
ER
Takagaki
Teresa Yae
TY
Soares
Fernando Augusto
FA
Capelozzi
Vera Luiza
VL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001938:Brazil; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000556:secondary*; D053379:Chromogranin A / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis*; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D007633:Keratins