The Ki-67 labeling index is not a useful predictor for the follow-up of cervical intraepithelial neoplasia 1.

OBJECTIVE: Our aim was to determine whether the Ki-67 immunostaining pattern, present on diagnosis of cervical intraepithelial neoplasia (CIN), predicts the change from low-grade to high-grade CIN over a 2-year period after diagnosis. MATERIALS AND METHODS: Of 59 cervical biopsy samples from 59 patients diagnosed as having cervical CIN, 35 were diagnosed as CIN 1 and 24 were diagnosed as CIN 2 or CIN 3. The Ki-67 immunostain showed immunopositive cells in the upper two thirds of the epithelium in all specimens. Two hundred nuclei were counted in 25 high-power fields in each specimen, including all of the epithelial layers, to determine the mean number of Ki-67-positive cells. In situ hybridization was used to demonstrate and type human papillomavirus. The chi test, Fisher exact test, Student t test, one-way analysis of variance, and Tukey test were used for statistical analysis, with significance set at p < .05. RESULTS: The mean Ki-67 labeling index for CIN 1, CIN 2, CIN 3, and CIN 2,3 were, respectively, 32.5%, 43.2%, 53.2%, and 47.8%. The statistical study showed significant differences between CIN 1 versus CIN 2, CIN 1 versus CIN 3, and CIN 1 versus CIN 2,3. For CIN 1, the mean Ki-67 labeling index was 32.8% when the lesion disappeared and was 34.6% for persisting lesions. There was no statistically significant difference. CONCLUSIONS: Ki-67 labeling index did not predict persisting CIN 1.

The 18q21 region in colorectal and pancreatic cancer: independent loss of DCC and DPC4 expression.

UNLABELLED: The 18q21 region is frequently altered in gastrointestinal tumors. Three candidate tumor suppressor genes have been identified in it: DCC, Smad4/DPC4 and Smad2; the mechanisms involving their inactivation have not been completely elucidated. In this study, genetic losses at 18q21 and expression of DCC and DPC4 in colorectal (n=12) and pancreatic (n=16) cell lines and in colorectal tissues (n=10) were analyzed. The status of the 18q21 region was assessed using microsatellite analysis and duplex PCR of exonic sequences; expression was analyzed by RT-PCR; mutational analysis of DPC4 cDNA was performed in selected cases. Homozygous losses of microsatellite markers at 18q21 were not observed in colon or pancreas lines; however, a higher proportion of apparent homozygosity than expected was found. DCC and DPC4 transcripts were detected in 11/12 and 12/12 colorectal cancer lines, respectively. In tumors, homozygous losses at 18q21 were detected in three cases, without affecting DCC. All tumors retained DCC and DPC4 mRNA expression. In pancreatic lines, DPC4 was inactivated through homozygous deletion (n=5), intragenic mutation (n=3), and lack of protein (n=2). IN CONCLUSION: (1) microsatellite analysis does not provide adequate information regarding homozygous losses at 18q21; (2) approximately 65% of pancreas cancer lines show inactivation of DPC4; and (3) loss of DCC and DPC4 occur independently.

Factors influencing the development of metabolic bone disease in primary biliary cirrhosis.

The prevalence, type, and factors that may influence the development of bone disease in primary biliary cirrhosis, have been investigated in 20 consecutive patients, who, in addition to liver function tests and mineral and vitamin D metabolism studies, were submitted to a transiliac bone biopsy after tetracycline double-labeling for quantitative histomorphometric examination. Intestinal calcium absorption was also assessed in 16 patients. Seven patients (35%) had reduced bone volume and were considered osteoporotic. Three also had bone mineralization impairment, but did not have criteria for osteomalacia. Bone formation was depressed in 15 patients, and bone resorption was low or normal in 19 cases. Eroded surfaces were reduced in all osteoporotic patients. Duration of primary biliary cirrhosis was significantly longer in patients with osteoporosis (6.3 +/- 0.6 yr) than in those without osteoporosis (2.6 +/- 0.6, p = 0.004). Moreover, osteoporosis was more prevalent in postmenopausal women, and in those who had intestinal calcium malabsorption, which was present in 80% of osteoporotic patients but in only 18% of nonosteoporotic patients (p = 0.03). Osteoporosis and mineralization bone impairment were unrelated to the severity of cholestasis. 25-Hydroxyvitamin D was significantly lower in those patients with intestinal calcium malabsorption. The results of this study indicate that osteodystrophy in primary biliary cirrhosis is characterized mainly by "low-turnover" osteoporosis, which is related to the duration of the liver disease, postmenopausal condition, and calcium malabsorption.