11p deletions and breakpoints in squamous cell carcinoma: association with altered reactivity with the UM-E7 antibody.

The UM-E7 monoclonal antibody raised against the UM-SCC-I human squamous cell carcinoma (SCC) cell line identifies a cell surface antigen that is strongly expressed in normal tissues. The locus (MICI) controlling the expression of E7 and related cell surface antigens has been mapped to chromosome band 11p13. This band has been identified as a region of cancer-associated aberrations and as the probable locus of a tumor suppressor gene. Although E7 antigen expression is strong in normal keratinocytes, it varies among squamous carcinoma cell lines. Some SCC lines (12/26) exhibit weak expression of the E7 antigen, whereas other SCC cell lines (14/26) and 21 cell lines from other tumor types express the antigen strongly. On the basis of these observations and of mapping data, we postulated that low E7 antigen expression in a subset of SCC cell lines might be associated with chromosomal rearrangement or deletion involving the E7 locus on 11p. Fully evaluable karyotypes were prepared from 19 SCC cell lines, including 11 with weak and eight with strong E7 expression. Eight of the 11 lines with weak E7 expression had 11p abnormalities. Four of these contained 11p deletions, and four others had a breakpoint in 11p. In contrast, none of the cell lines in the group with strong E7 expression had an 11p deletion, although one had a rearrangement with an 11p breakpoint. In the four tumors with visible 11p deletions, the smallest region of overlap corresponded to the 11p13-p14 region. The mean log10 50% endpoint E7 titer in the group with 11p deletions or breakpoints was nearly two orders of magnitude lower than that of the lines with no 11p abnormality (1.95 +/- 0.53) (P less than 0.02). Our results indicate that the UM-E7 antibody identifies tumors with 11p13-p14 deletions and other 11p rearrangements and that the 11p region is a site of nonrandom chromosome rearrangement in a subset of human squamous cancers. The strong association of loss of antigen expression with visible 11p deletion or rearrangement in some tumors suggests that other tumors with this phenotype may contain submicroscopic lesions of 11p13-p14.

Effects of the antiestrogen toremifene on growth of the human mammary carcinoma cell line MCF-7.

The effects of toremifene, a new antiestrogenic drug, were investigated in vitro on the exponentially growing human mammary carcinoma cell line MCF-7. The drug effects were monitored by serial cell counts and DNA flow cytometry. The inhibitory effect of toremifene on MCF-7 became greater as the drug concentration was increased from 1 microM to 10 microM. At 5 microM toremifene induced a large decrease in the relative percentages of S- and G2/M-phase cells, and an increase in the amount of cell debris, indicating increased cell death. After withdrawal of the drug the mammary cancer cells resumed logarithmic growth similar to that of control cells. The effects caused by toremifene were similar to those caused by tamoxifen both in quality and quantity.

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck.

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.

Production of a monoclonal antibody (K 931) to a squamous cell carcinoma associated antigen identified as the 17-1A antigen.

During our efforts to develop monoclonal antibodies (MAbs) to tumor associated surface antigens of squamous cell carcinomas of the head and neck, monoclonal antibody K 931 was produced. The high affinity antibody (Ka 5.0 x 10(10) M-1) showed reactivity with 58 out of 62 squamous cell carcinomas of the head and neck. In contrast normal squamous epithelium as found in epidermis, oral cavity, epiglottis, pharynx, larynx and esophagus did not express the antigen. All other tested epithelial (simple and transitional) tissues did express the antigen, but non-epithelial tissues were negative. Further characterization revealed that the antigen represents the 17-1A antigen. A not earlier reported, enhanced expression of the 17-1A antigen was observed among some primary and all metastatic SCC.