Identification of immunohistochemical prognostic markers for survival after resection of pulmonary metastases from colorectal carcinoma.
BACKGROUND
Although aggressive resection of pulmonary metastases prolongs the survival of patients with metastatic colorectal cancer, there is a need for predictive pathologic parameters to understand the key molecular events of metastatic progression. The aim of this study was to verify immunohistochemical markers in addition to established clinical parameters after surgery.


METHODS
From our subset of patients undergoing resection of pulmonary metastases from metastatic colorectal carcinoma, we analyzed 39 patients (23 men and 16 women) between 2003 and 2007. Only patients who met the criteria for a potentially curative operation were included. All patients were analyzed with regard to age and sex, primary tumor location, stage of the primary tumor, history of hepatic metastases, number of pulmonary metastases, pre-thoracotomy carcinoembryonic (CEA) serum antigen level, and the presence of thoracic lymph node metastasis. Furthermore, we immunohistochemically investigated the expression of vascular endothelial growth factor (VEGF)-D, FBJ murine osteosarcoma viral oncogene homolog B (FOS-B), and melanoma antigen (MAGE)-A in the surgical specimens of pulmonary metastatic lesions.


RESULTS
The overall 3-year survival was 50.6 %. A significantly longer survival was observed with multivariate analysis in patients with a pre-thoracotomy serum carcinoembryonic antigen level of no more than 4.2 ng/mL ( P = 0.001), and Dukes stage A or B primary tumor ( P = 0.001). A significantly longer recurrence-free survival was observed with multivariate analysis in patients without thoracic lymph node involvement compared to patients with pulmonary and/or mediastinal lymph node metastases ( P = 0.006). The stage of the primary tumor remained significant ( P = 0.029), and FOS-B expression in tumor cells showed a trend towards favorable recurrence-free survival after pulmonary metastasectomy ( P = 0.059). No statistically significant difference was found in the overall survival rate or recurrence-free survival rate of patients with expression of VEGF-D or MAGE-A antigen in pulmonary metastatic tumor cells.


CONCLUSIONS
Our results suggest that in addition to clinically prognostic factors, FOS-B expression has a debatable impact on patient survival. We conclude that the evaluation of molecular and clinical prognostic parameters at the time of pulmonary metastasectomy offers a greater understanding of the metastatic process and provides important information for patient selection.
Pfannschmidt
J
J
Thoracic Surgery, Thoraxklinik am Universitätsklinikum, 69126 Heidelberg, Germany. joachim.pfannschmidt@thoraxklinik-heidelberg.de
Bade
S
S
Hoheisel
J
J
Muley
T
T
Dienemann
H
H
Herpel
E
E
D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000401:mortality*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D018570:Risk Assessment; D013908:Thoracotomy / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C064269:FOSB protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; D042643:Vascular Endothelial Growth Factor D