Lymphatic invasion and nodal
metastasis are predictors of shorter disease-free and overall survival in
carcinoma of the uterine cervix. The
monoclonal antibody D2-40, which reacts with the oncofetal membrane
antigen M2A, is a new selective marker for lymphatic endothelium, and has been shown to be useful in identifying the presence of lymphatic invasion in various
malignant neoplasms, including cervical
carcinoma. However, the reactivity of the
tumor cells with D2-40 has not yet been evaluated. In this study, we examined the pattern of D2-40 immunoreactivity in a series of 138 invasive
squamous cell carcinomas of the uterine cervix. We correlated the presence and extent of D2-40 immunoreactivity in the
tumor cells with various clinicopathologic features, the presence of lymphatic invasion,
lymph node metastasis and outcome. Diffuse or focal D2-40 immunoreactivity was present in 17 (12%) and 81 (59%)
tumors, respectively, while 40 (29%)
tumors showed no immunoreactivity. Lymphatic invasion and nodal
metastasis were present in 56 and 29% of
tumors, respectively.
Tumor emboli within lymphatic spaces and metastatic
tumor foci in lymph nodes showed no immunoreactivity in 86 and 80% of the cases, respectively. Lymphatic invasion and nodal
metastasis were significantly more common in
tumors showing low D2-40 immunoreactivity (P<0.0001 and 0.022, respectively). D2-40 immunoreactivity showed no correlation with any other clinicopathologic features examined, including
tumor size, grade and FIGO stage. In univariate analysis low D2-40 immunoreactivity was significantly associated with shorter recurrence-free, but not with overall survival. Our studies suggest that D2-40 immunostaining may serve as a marker for increased risk of lymphatic invasion and
tumor recurrence in cervical biopsy material. Further study of the
biological function of the M2A
antigen may shed some light on the interaction of
tumor cells with lymphatics.