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Abstract

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.

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Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

Alvimar G. Delgado, B U Sevin, B Bundy … (1990)

There were 732 evaluable patients with primary, previously untreated, histologically confirmed stage I squamous carcinoma of the cervix with greater than or equal to 3-mm invasion. Of these, 645 had no gross disease beyond the cervix/uterus, had negative paraaortic lymph nodes, and had undergone a radical hysterectomy with pelvic lymphadenectomy. The 3-year disease-free interval (DFIs) for the 545 patients with negative pelvic nodes was 85.6%, and for the 100 with positive pelvic nodes, 74.4%. A large number of pelvic nodes involved with tumor was not correlated with a poorer prognosis; the DFIs were 72.1, 86.4, and 64.6% for one, two, and three or more positive pelvic nodes, respectively. DFI correlated strongly with depth of tumor invasion, both in absolute terms (mm) and infractional thirds. The DFI was 94.6% for less than or equal to 5 mm, 86.0% for 6-10 mm, 75.2% for 11-15 mm, 71.5% for 16-20 mm, and 59.5% greater than or equal to 21 mm. In fractional terms, the DFI was 94.1% for superficial third, 84.5% for middle third, and 73.6% for deep third invasion. With respect to clinical tumor size, the DFIs were 94.8, 88.1, and 67.6% for occult, less than or equal to 3 cm, and greater than 3 cm, respectively. The DFI was 77.0% for those with positive capillary-lymphatic spaces (CLS) and 88.9% for those with negative CLS. Tumor grade and parametrial status correlated with DFI. DFI was not significantly different for age, disease status of the surgical margins, tumor description (e.g., exophytic), quadrant involved with tumor, uterine extension, and keratinizing status of tumor cells. Clinical tumor size, CLS, and depth of tumor invasion were independent prognostic factors.

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Mucin-type glycoproteins.

Ger J. Strous, René Dekker (1991)

Considerable advances have been made in recent years in our understanding of the biochemistry of mucin-type glycoproteins. This class of compounds is characterized mainly by a high level of O-linked oligosaccharides. Initially, the glycoproteins were solely known as the major constituents of mucus. Recent studies have shown that mucins from the gastrointestinal tract, lungs, salivary glands, sweat glands, breast, and tumor cells are structurally related to high-molecular-weight glycoproteins, which are produced by epithelial cells as membrane proteins. During mucin synthesis, an orchestrated sequence of events results in giant molecules of Mr 4 to 6 x 10(6), which are stored in mucous granules until secretion. Once secreted, mucin forms a barrier, not only to protect the delicate epithelial cells against the extracellular environment, but also to select substances for binding and uptake by these epithelia. This review is designed to critically examine relations between structure and function of the different compounds categorized as mucin glycoproteins.