Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer.
OBJECTIVE
To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer.


METHODS
We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosin-stained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis.


RESULTS
Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (>or= 40), high lymphatic vessel density (>or= 9), high Ki-67 labeling index (>or= 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis. A combined examination with four independent immunohistochemical markers (microvessel density, cathepsin D, lymphatic vessel density, and MUC1) revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis.


CONCLUSIONS
Analysis of a combination of immuno-histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
Iwao
I
Kaneko
Shinji
S
Tanaka
Shiro
S
Oka
Shigeto
S
Yoshida
Toru
T
Hiyama
Koji
K
Arihiro
Fumio
F
Shimamoto
Kazuaki
K
Chayama
D014408:Biomarkers, Tumor / Q000032:analysis*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008207:Lymphatic Metastasis / Q000473:pathology*; D011379:Prognosis
D014408:Biomarkers, Tumor