Low intercellular adhesion molecule 1 and high 5T4 expression on tumor cells correlate with reduced disease-free survival in colorectal carcinoma patients.

The purpose of this study was to investigate the prognostic value of the expression of intercellular adhesion molecule 1 (ICAM-1), leukocyte function antigen 3 (LFA-3), human leukocyte differentiation antigen (HLA)-ABC, HLA-DR, and 5T4 with regard to disease-free survival in Dukes' B and C colorectal carcinoma patients. Forty-one patients (28 Dukes' B and 13 Dukes' C) were entered into this study. Immunocytochemistry was performed on cytospin preparations of enzymatically digested colorectal carcinoma cell suspensions. The frequency of metastases and the duration of disease-free survival were compared between the 25% lowest expressers and the 75% remaining patients for ICAM-1, LFA-3, HLA-ABC, and HLA-DR, and between the 25% highest expressers and the 75% remaining patients for 5T4. Low numbers of ICAM-1-expressing tumor cells were associated with a shorter disease-free survival (P < 0. 001), independent of Dukes' stage. High numbers of 5T4-expressing tumor cells were associated with shorter disease-free survival in Dukes' B patients (P = 0.04). Cox proportional hazard analysis indicated that low numbers of ICAM-1(+) and high numbers of 5T4(+) cells were independent prognostic factors with relative risks of 13. 0 (P = 0.0002) and 4.7 (P = 0.02), respectively. The combination of 5T4 and ICAM-1 marker information identified subgroups of patients with a good (high ICAM-1) or poor (low ICAM-1/high 5T4) prognosis. Neither a lack of HLA-ABC and LFA-3 expression nor the presence of HLA-DR on the tumor cells gave additional prognostic information. These findings demonstrate that low ICAM-1 and high 5T4 expression on tumor cells are prognostic markers, additional to Dukes' stage, for reduced disease-free survival in Dukes' B and C colorectal carcinoma patients.

Mucin-1-related T cell infiltration in colorectal carcinoma.

Mucins (MUC) are highly glycosylated molecules widely expressed on epithelia of different origins, including colonic mucosa. Altered glycosylation processes in tumour cells result in the exposure of normally cryptic peptide epitopes, which may then be recognized as tumour-specific antigens. Recently, MUC1-specific antibodies were detected in the serum of a broad range of cancer patients, and from different tumours tumour-specific cytotoxic T lymphocytes (CTL) were isolated that recognized MUC1. Absence of HLA restriction in the recognition has been ascribed to the highly repetitive sequence of the polypeptide core, allowing simultaneous recognition of multiple identical epitopes and cross-linking and aggregation of T cell receptor on mucin-specific T cells. We investigated the expression of MUC1 epitopes in 56 cell suspensions from Dukes' B to D colorectal carcinomas using antibodies that recognize distinct peptide sequences on the glycosylated or deglycosylated MUC1 protein backbone. No relation was observed between MUC1 expression, or the extent of its glycosylation, and Dukes' stage, tumour location and tumour differentiation, but a positive correlation was detected between the percentages of tumour cells expressing mucin-1 and the numbers of CD3+ infiltrating cells. These tumour-infiltrating lymphocytes contained, however, only a few MUC1-specific T lymphocytes, as CTL showing preferential killing of MUC1-expressing target cells were only obtained from one tumour. Since, in addition, the majority of colorectal carcinomas were found to express the fully glycosylated MUC1 glycoprotein, its potential role as a target antigen for T-lymphocyte-mediated immunotherapy in this tumour type is probably limited.

Prevalence of Chlamydia trachomatis infection in a population of asymptomatic women in a screening program for cervical cancer.

The prevalence of Chlamydia trachomatis infection in a population of women with no symptoms of sexually transmitted disease was investigated. These women, aged 35-55 years, participated in a screening program for cervical cancer. With the use of a direct immunofluorescence method, 109 out of 2,470 smears tested were positive for Chlamydia trachomatis, indicating an overall prevalence of 4.4%. No changes in prevalence were found when five-year cohorts of this group were analyzed, indicating that age-dependent changes or epidemiological factors do not result in a different (decreased) prevalence over the ages 35 to 55 years. The prevalence of Trichomonas vaginalis and fungi, as detected by cytological screening, was lower than that observed for Chlamydia trachomatis: 3.1 and 2.1%, respectively. Of the 109 smears positive for Chlamydia trachomatis, 90 showed cervical cells with reactive changes (out of 1,490 smears with PAP II), whereas no cytological changes were found in 15 cases (out of 884 smears with PAP I). Changes suggestive of mild or moderate dysplasia were found in only four cases (out of 93 smears with PAP III). The results indicate that Chlamydia trachomatis is associated with reactive changes of endocervical cells and raise serious questions about whether prevention of possible secondary effects such as infertility and pelvic inflammatory disease can be achieved by a combined screening program for cervical cancer and Chlamydia trachomatis.