Computerized image cytometric analysis of: KI-67 and BCL-2 markers in: benign endometrial hyperplasia and endometrial carcinoma

The normal endometrium is a tissue subjected to rapid cycling proliferation and differentiation followed by breakdown under hormonal influences .Endometrial hyperplasia [EH], which is a frequent disorder seen in majority of endometrial biopsy samples, embraces a group of lesions with different biological potential with tendency to progress into endometrial adenocarcinoma [EC]. The reproducibility of the histopathologic diagnosis of endometrial hyperplasia is poor as regarding intra and inter observer errors as well as the over and under diagnosis of malignant changes. Strict criteria, good sampling and use of additional ancillary molecular techniques are expected to improve the sensitivity and accuracy of this diagnosis. To evaluate the immnohistochemical expression of Ki-67 and Bcl-2 in various types of endometrial hyperplasia versus endometrioid variant of endometrial adenocarcinoma. 2-To correlate the immunohistochemical expression with grade and stage of EC and 3-To evaluate the prognostic value of morphometric D-score in prediction of endometrial hyperplasia- cancer progression. Paraffin embedded-tissue specimens obtained from 57 female patients were studied. Cases were categorized into the following groups: Control group [5 cases of normal proliferative endometrium], fifteen cases of various degrees of hyperplastic lesions including 10 cases of [EH] and 5 cases of intra epithelial neoplasia [EIN]. Fifteen cases of combined lesions [EH+EIN+grade 1EC] and lastly 22 cases of various grades of endometrioid variant of EC. All 57 studied cases were subjected to:Immunohistochemical staining for Ki-67 and Bcl-2 markers. The percent of positivity was calculated using computerized image cell analysis. In addition computerized morphometric analysis for D-score calculation were performed on standard diagnostic hematoxylin and eosin [H and E] stained sections of all cases of endometrial hyperplasia. Normal proliferative endometrim [5 cases, 100%] expressed high score of both Ki-67 and Bcl-2 markers. Also, in the hyperplastic group; the peak immunoreactivity for Ki-67 was seen in the EIN subgroup [5/5,100%]. In contrast, Ki-67 immunoreactivity was seen in only 80% of EH subgroup. However, the difference was statistically insignificant [p>0.05]. KI index was higher in carcinoma compared to EH. The difference between both groups was statistically significant [p=0.001]. Bcl-2 immunopositivity was seen in three cases of EIN [60%] and eight cases of EH cases [80%].Endometrial carcinoma showed Bcl-2 expression in [11 out of 22 cases50%]. Bcl-2 was expressed in the majority of cases of EH [8 cases out of 10 cases 80%] and showed uniform glandular positivity, but it was diminished in EIN subgroup [2 out of 5 cases, 60%]. Ki-67 was expressed in the majority of endometrial adenocarcinoma [20/22 cases, 90.9%]. Bcl-2 expression was decreased as the grade increased but this relation was statistically insignificant [p=>0.05]. Ki-67 and Bcl-2 scores were found to be negatively correlated in the same histologic group and this inverse relation was statistically significant [p=0.00]. Finally, D-score calculation revealed that: D-score value was more than 1 in cases of EH and less than 1 in EIN cases and the cut off value was 2.33. Normal proliferative endometrium expressed high levels of both Ki-67 and Bcl-2. It was shown also, that Ki-67 was sequentially increased from EH through EIN to EC. In contrast, Bcl-2 positivity was decreased significantly in cases of EC mainly the high grades. Such inverse relation between both markers [Ki-67and Bcl-2] was proved to be statistically significant. The imbalance between proliferation and apoptosis may be an important factor in the development of different endometrial lesions; benign and malignant. Precancerous endometrial lesions [EIN] could be identified, by using morphometric analysis for D-score calculation based on combination of architecture and cytological features with consideration to volume percentage stroma parameter

rabbit nasal mucosa under the effect of intranasal insulin: histological study

The histopathological changes occurred in the rabbit mucosa under the effect of a conventional intranasal humanized insulin preparation [NI], given a properly calibrated dose, were studied. The duration of administration was one week [6 rabbits SG1], 2 weeks [6 rabbits, SG2] and 4 weeks [6 rabbits, SG3]. Another three comparable groups [EG1, EG2 and EG3], each composed of three rabbits which received the enhancer alone intranasally for the same durations, respectively, were alone studied. The changes encountered in the nasal mucosa of the studied groups were compared with the control mucosa supplied by three normal rabbits. The reported changes were related to the period of exposure. On more prolonged exposure, as in SG3, the outst and ing features were abrupt surface keratinization, hypertrophy of the mucosal nerve bundles, hyperplasia of the gl and ular units, and perivascular edema. In comparison with the control nasal mucosa no changes could be detected in the corresponding EG1, EG2 and EG3. Thus, these changes were induced by the given insulin and attributed to its local antigenic and /or chemical irritation property rather than a metabolic one. Provocation of severe pain by NI was also suggested on prolonged administration