Young-age onset of colorectal cancer in Israel.

AIM: The study was conducted to investigate the differences in clinical-pathological, ethnic, and demographic presentations and the expression of mismatch repair proteins in a cohort of young-onset (50 years) with colorectal cancer. MATERIALS AND METHODS: Clinical, demographic, and histopathological data of patients with colorectal cancer were collected retrospectively from medical records and pathology reports. RESULTS: Ninety patients, 50 years of age or younger with a mean age of 42 years were compared with a group of 190 patients above 50 years of 50 (see Table 1). Sixty percent of the young-onset patients were females, compared to 40% in the older age group (P = 0.02). Twenty-one percent of the young-onset patients were Arabs as compared to 2% of older-onset patients (P = 0.001). Younger patients displayed a higher percentage of mucinous cancers and a higher percentage of diagnosis at an advanced stage of disease; 40% of young-onset versus 31% of older-onset patients presented Duke's stages C and D (P = 0.02). CONCLUSIONS: Younger age of onset colorectal cancer in our cohort of Israeli patients is associated with higher percentage of Arab patients, mucinous cancers, female gender, and advanced stage at diagnosis.

Suppressive effect of aspirin on aberrant crypt foci in patients with colorectal cancer.

BACKGROUND: and aims: Aspirin and other non-steroidal anti-inflammatory drugs have been shown to reduce the risk of colorectal cancer (CRC). Animal models have shown that aspirin is also effective in reducing the density of aberrant crypt foci (ACF). The aim of the study was to evaluate the effect of chronic administration of aspirin on the distribution pattern and histological characteristics of ACF in patients with CRC. METHODS: Our study compared the distribution patterns and histomorphological characteristics of ACF between a group of CRC patients treated with low dose aspirin (n=59) and a control group without aspirin (n=135). ACF were visualised on methylene blue stained macroscopically normal mucosa, microdissected, and serially cut. RESULTS: ACF were found in 75.8% of mucosal samples from the control group and in 36% of mucosal samples from the aspirin treated group, indicating a 47% decline in prevalence of ACF in colonic samples of patients treated with aspirin. A significant reduction from 92.5% to 40% (p<0.0001) was found in distal large bowel samples containing one or more ACF. Similarly, the aspirin treated group showed a reduction in ACF density of 64% and 82%, respectively, in both proximal and distal parts of the colon, indicating a significant reduction in ACF/cm(2) in distal colon samples (p<0.01). The aspirin treated group displayed a 52% reduction in dysplastic ACF although this difference was not statistically significant. CONCLUSIONS: Our study has provided evidence of the effective chemopreventive action of low dose aspirin on ACF in humans.

Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon.

BACKGROUND: One of the first steps in multistage colonic carcinogenesis is increased cell proliferation and an upward shift of the proliferation zone of colonic crypts. In the present study, progression in cell kinetics was followed up at all sequential stages of colonic carcinogenesis, starting with aberrant crypt foci (ACF), the earliest putative preneoplastic lesions, hyperplastic and dysplastic polyps, and invasive carcinomas. MATERIALS AND METHODS: Colonic tissue and tumor specimens were prospectively obtained from 65 patients treated at our hospital for adenocarcinoma or malignant polyps. For identification of ACFs, dissected mucosal strips obtained from patients with colorectal cancer were stained with 0.1% methylene blue and scanned under dissecting microscope. Paraffin-embedded ACFs and macroscopic lesions were serially sectioned, deparaffinized, and stained with a monoclonal antiproliferating cell nuclear antigen (PCNA) antibody. The PCNA-labelling index (PCNA-LI), expressed as a ratio of positively stained nuclei to total nuclei counted, was calculated separately for basal, middle, and upper colonic crypt compartments. A comparison of the PCNA-LI was made for each compartment in normal mucosa, and hyperplastic and dysplastic lesions. RESULTS: A stepwise increase in the PCNA-LI was observed during neoplastic progression of colonic lesions. The two most important variables of increased cell proliferation, expressed as PCNA-LI per crypt compartment, were the presence of dysplasia and the size of dysplastic lesions. CONCLUSIONS: In colorectal carcinogenesis, hyperproliferation with upward expansion of proliferative compartment is a characteristic feature at all stages of malignant progression.