Integrin beta-3 L33P: a new insight into the pathogenesis of chronic oxaliplatin-induced peripheral neuropathy?

AIM: To assess the significance of the ITGB3 polymorphism at residue 33 (ITGB3 L33P) in the development of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN). METHODS: Fifty-five patients with advanced colorectal cancer were genotyped, using allele-specific primers and sybr green in real-time PCR. Patients had received adjuvant oxaliplatin-based chemotherapy. The severity of the OXLIPN was defined by means of the clinical total neuropathy score (TNSc). Following the discontinuation of treatment, 34/55 patients (61.8%) developed OXLIPN. Grade I neurotoxicity was revealed in 13 (38.2%) patients and grade II neurotoxicity in 21 (61.8%) patients. RESULTS: Patients without OXLIPN (n = 21) were 19% homozygous for C, 33.3% were heterozygous, and 47.7% were homozygous for T. The corresponding percentages for patients developing any grade of OXLIPN (n = 34) were similar. About half of patients (46.1%) with grade I OXLIPN were heterozygotes (CT), 23.1% were CC, and 30.8% were TT. The majority of patients with grade II OXLIPN were TT (66.7%) with the remaining 33.3% being CT. The TT genotype was associated with increased severity of OXLIPN compared to the genotypes containing the C allele (P = 0.044). CONCLUSION: The ITGB3 L33P seems to be unrelated to the development of OXLIPN, but it appears to be related to its severity.

Cognitive Decline and Modulation of Alzheimer's Disease-Related Genes After Inhibition of MicroRNA-101 in Mouse Hippocampal Neurons.

MicroRNAs have emerged as regulators of brain development and function. Reduction of miR-101 expression has been reported in rodent hippocampus during ageing, in the brain of Alzheimer's disease (AD) patients and in AD animal models. In this study, we investigated the behavioral and molecular consequences of inhibition of endogenous miR-101 in 4-5-month-old C57BL/6J mice, infused with lentiviral particles expressing a miR-101 sponge (pLSyn-miR-101 sponge) in the CA1 field of the hippocampus. The sponge-infected mouse model showed cognitive impairment. The pLSyn-miR-101 sponge-infected mice were unable to discriminate either a novel object location or a novel object as assessed by object place recognition (OPR) and novel object recognition (NOR) tasks, respectively. Moreover, the sponge-infected mice evaluated for contextual memory in inhibitory avoidance task showed shorter retention latency compared to control pLSyn mice. These cognitive impairment features were associated with increased hippocampal expression of relevant miR-101 target genes, amyloid precursor protein (APP), RanBP9 and Rab5 and overproduction of amyloid beta (Aß) 42 levels, the more toxic species of Aß peptide. Notably, phosphorylation-dependent AMP-activated protein kinase (AMPK) hyperactivation is associated with AD pathology and age-dependent memory decline, and we found AMPK hyperphosphorylation in the hippocampus of pLSyn-miR-101 sponge mice. This study demonstrates that mimicking age-associated loss of miR-101 in hippocampal neurons induces cognitive decline and modulation of AD-related genes in mice.

EGFR, HER-2 and COX-2 levels in colorectal cancer.

AIMS: Receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER-2 and cyclooxygenase-2 (COX-2) are promising molecular targets for cancer therapy and/or prevention. The aim was to evaluate EGFR, HER-2 and COX-2 mRNA and protein expression in colorectal cancer patients. METHODS AND RESULTS: EGFR, HER-2 and COX-2 protein levels were evaluated by immunohistochemistry in malignant tissue, dysplastic tissue and normal mucosa samples from 124 cases with primary colorectal carcinoma. Moreover, the corresponding mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction in 46 colorectal carcinomas. There was strong correlation between mRNA and protein expression for EGFR (P < 0.001), HER-2 (P < 0.004) and COX-2 (P < 0.007). EGFR levels did not correlate with stage of the disease or tumour differentiation. HER-2 and COX-2 levels increased in advanced stages and in differentiated carcinomas. Furthermore, a correlation between HER-2 and COX-2 expression was revealed in neoplastic tissue. CONCLUSIONS: EGFR as well as HER-2 and COX-2 overexpression represent important alterations that are related to the molecular pathways underpinning colorectal carcinogenesis. Further investigation is required to evaluate the impact of these markers on the management of patients with colorectal cancer.

Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas.

PURPOSE: MicroRNAs are evolutionarily conserved non-coding components of the transcriptome that can post-transcriptionally control gene expression. Altered microRNA expression has been found to be a common feature of several cancers, including lung carcinomas. The biogenesis and maturation of microRNAs is known to be mediated by the ribonucleases Drosha, Dicer and Ago2. The purpose of the present study was to investigate the expression and distribution of Drosha, Dicer and Ago2 in human non-small cell lung carcinomas (NSCLC) and to relate the respective expression patterns to clinocopatholical features. METHODS: We used five human NSCLC-derived cell lines and primary formalin-fixed paraffin-embedded tissue samples from 83 NSCLC patients. Drosha, Dicer and Ago2 mRNA and protein expression levels, and their sub-cellular distributions, were assessed using RT-PCR, Western blotting, immunofluorescence and immunohistochemistry, respectively. RESULTS: We found that Drosha, Dicer and Ago2 were expressed in all the cell lines and primary neoplastic and non-neoplastic tissue samples tested. The intensity of the immunohistochemical staining was found to be significantly lower in stage I tumors compared to normal lung tissues. Dicer expression was found to be significantly higher in stage II compared to stage I tumors, and in stage III compared to stage II and stage I tumors. CONCLUSIONS: Our results point at a role of Drosha, Dicer and Ago2 in the development of NSCLC and suggest that Dicer may be implicated in the progression of these tumors to advanced stages.

Presence of immunoreactive corticotropin-releasing hormone in human endometrium.

Immunoreactive CRH (IrCRH) is produced locally in experimentally induced and spontaneous inflammation. Where it exerts autocrine or paracrine proinflammatory effects. In addition, CRH is secreted by the human placenta, rat Leydig cells, and rat and human ovaries, where it may participate in the inflammatory processes of ovulation and luteolysis, and/or the regulation of steroidogenesis. Finally, CRH is secreted in vitro by cultured human epithelial and decidualized stromal endometrial cells. To investigate the presence of CRH in human endometrium in vivo, we examined this tissue immunohistochemically and by extraction/RIA using a polyclonal, highly specific antirat/human CRH antibody. Endometrial biopsies from 33 women, aged 23-43 yr (median age, 33.5 yr), were performed by linear endometrial curettage for diagnostic purposes at different stages of the cycle. Intense IrCRH staining was localized in the cytoplasm of cells of the endometrial glands in all samples examined. IrCRH was also found in endometrial stromal cells exhibiting decidual reaction and in local immune accessory cells. The mobility of the endometrial IrCRH molecule was similar to that of r/hCRH in reverse phase high pressure liquid chromatography. The presence of CRH in the endometrium, and more specifically in the glandular epithelium during the proliferative and secretory phases of the menstrual cycle together with its known proinflammatory properties, suggest that this neuropeptide might participate in the inflammatory-like phenomena of endometrial physiology, such as menstrual shedding, surface epithelium repair, and/or implantation of the blastocyst. The presence of CRH in decidualized stromal cells is in accordance with its previously reported production by in vitro decidualized cultured endometrial stromal cells as well as by the placental decidua.

Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries.

Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also present in human ovaries, we examined ovaries from normal women and patients with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutea. No IrCRH was present in oocytes of primordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent from the stroma or the sparsely present corpora lutea and was clearly detected in oocytes of primordial follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries was higher than that in polycystic ovaries (mean +/- SD, 0.075 +/- 0.02 vs. 0.038 +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid samples collected from women undergoing ovarian hyperstimulation for assisted reproduction had low, but detectable, levels of IrCRH (mean +/- SD, 4.975 +/- 1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH is present in normal human ovaries and follicular fluid, suggesting that this neuropeptide may play a regulatory role in one or more of the various functions of this gonad, such as ovulation and/or luteolysis, through its proinflammatory properties and/or its auto/paracrine regulation of steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localization in primary oocytes of polycystic ovaries may be related to the increased androgen biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in women with the polycystic ovarian syndrome, respectively.

Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats.

BACKGROUND: This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats. STUDY DESIGN: One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. RESULTS: Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I. CONCLUSIONS: Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.

bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with rectal cancer.

Combined radiation therapy and chemotherapy are adjuvant treatments given after surgery to patients with rectal carcinoma. Because apoptosis seems to play a role in tumor response to radiotherapy, the current study investigates whether there is a correlation between the ratio of bcl-2 oncoprotein and bax expression in rectal adenocarcinoma and the clinical response to radiotherapy. Elective colectomy for primary rectal adenocarcinoma followed by adjuvant radiotherapy and chemotherapy was performed on 35 patients. Tumors were staged as B2 (n = 30) and C (n = 5), and were classified as radiation resistant (n = 19, group A) and radiation nonresistant (n = 16, group B). Immunohistochemical study, using the streptavidin-biotin complex technique and monoclonal antibody to bcl-2 and polyclonal antibody to bax protein was used on paraffin sections. Cases were considered positive if at least 5% of tumor cells displayed cytoplasmic staining for bcl-2 or bax. In each tumor, the bcl-2/bax ratio was calculated dividing the percentage of bcl-2-positive cells by the percentage of bax-positive cells. For statistical analysis, the Mann-Whitney rank sum test and Kruskal-Wallis analysis of variance test were used. Rectal tumors of group A displayed significantly greater bcl-2 immunoreactivity (40.2 +/- 4.2) compared with group B (20.2 +/- 3.8). In contrast, expression of bax protein was less in group A (30.3 +/- 3.3) compared with group B (41.3 +/- 2.3). The bcl-2/bax ratio was greater in group A (1.3 +/- 0.1) compared with group B (0.49 +/- 0.1), and was correlated with poor responsiveness to radiotherapy. The current study indicates that in patients with rectal carcinoma an elevated bcl-2/bax ratio in tissue specimens suggests increased tumor resistance to adjuvant radiotherapy. Thus, in such patients, the bcl-2/bax ratio may serve as a potential molecular marker for prediction of tumor prognosis.

Smooth muscle tumors of the gastrointestinal tract. A 10-year experience.

Benign or malignant smooth muscle tumors of the gastrointestinal tract are uncommon. The diagnostic and therapeutic approaches vary depending on the histological behavior of these neoplasms. Between 1981 and 1991, 32 patients with gastrointestinal tumors were treated at the Department of Surgery of the University of Patras. There were 16 females and 16 males. The mean age at the time of diagnosis was 61.9 years (range 22-83 years). Eighty-one per cent of the tumors were discovered in asymptomatic patients by a variety of diagnostic studies. Fifty-six per cent of tumors were located in the stomach, 38% in the small intestine and 6% in the colon. Leiomyomas made up 71.8% of these tumors and were treated by conservative excision. The malignant smooth muscle tumors were treated by radical excision in four cases and conservative excision in one case. The 5-year survival rate was 85% for leiomyomas and 0% for malignant smooth muscle tumors. There is widespread agreement that wide resection of the lesion is the appropriate treatment for these tumors. The size and mitotic activity of these tumors remain the most important diagnostic parameters and prognostic factors.

Radical consequence in the sexuality of male patients operated for colorectal carcinoma.

Sixty sexually-active male patients affected by colorectal cancer and surgically treated at the Department of Surgery at University of Patras between 1981 and 1987 were interviewed by structured questionnaire to evaluate the etiology of sexual dysfunction. Patients were divided into three groups: (1) 20 patients, mean age 60.5 years (range 39-70), subjected to high anterior resection for carcinoma of the sigmoid colon (not lower than 18 cm from the anal margins, 1.2% Dukes' A, 31% Dukes' B, 67.8% Dukes' C); (2) 20 patients, mean age 62.4 years (range 43-70), subjected to low anterior resection (not more than 8 cm from the anal margins, 3% Dukes' A, 36% Dukes' B, 61% Dukes' C); and (3) 20 patients, mean age 59.75 years (range 27-70), subjected to abdominoperineal surgery (Miles' technique) in whom the malignancy was in the distal rectum (8% Dukes' A, 32% Dukes' B, 60% Dukes' C). The first group served as the control. All the anastomoses in the low anterior resection group were performed by manual suture. Statistical evaluation of the three groups was by the chi 2-test. The form of sexual dysfunction, (1) cessation of sexual relationship, (2) absence of erection, (3) impossible penetration or (4) absence of ejaculation, varied according to the type of operation, the frequency of each form being 5%, 5%, 30%, 20% for the high anterior resection, 65%, 45%, 60%, 50% for Miles' operation and 20%, 25%, 45%, 5% for the low anterior resection respectively.

Nuclear grooves in fine needle aspiration (FNA) biopsies of breast lesions.

The present study was undertaken to evaluate the significance of grooved nuclei as an additional diagnostic criterion for primary breast carcinoma as well as their association with tumor grade in cytologic material obtained by fine needle aspiration (FNA). Cytologic slides of 105 cases of breast carcinoma (89 ductal, 10 lobular, 3 medullary, 3 mucinous) and 39 cases of benign lesions were reviewed. Histologic confirmation was obtained in all cases. In each case the number of grooved nuclei per 200 well-preserved cells per slide was recorded. Nuclear grooves were found in 62% (65/105) of the malignant and in 36% (14/39) of the benign lesions. This cytomorphologic feature was observed in all histologic types of breast carcinoma. Furthermore, nuclear grooves were present in all grades of ductal carcinoma, and at about the same frequency. Our findings indicate that in the mammary gland nuclear grooving cannot be considered as a criterion of malignancy, and is not helpful either in differentiating the various histologic types or in grading breast tumors in FNA preparations.

Microvessel density, proliferating activity, p53 and bcl-2 expression in in situ ductal carcinoma of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of lesions that show important differences in biologic behavior. New vessel formation has been reported as a prognostic indicator in breast carcinoma, but little information is available about its significance in DCIS. This study was planned to examine angiogenesis in DCIS in relation to histologic subtype, proliferation activity, p53 and bcl-2 expression. MATERIALS AND METHODS: Paraffin sections from 24 cases of DCIS (9 comedo and 15 non comedo type) were studied immunohistochemically using polyclonal and monoclonal antibodies to von Willebrand factor, Ki-67, p53 (clone 1801) and bcl-2 proteins. The streptavidine-biotin technique with microwave antigen retrieval was employed. RESULTS: Most cases showed enhanced microvessel formation around ducts with DCIS compared to normal ducts. Comedo carcinomas (CCs) showed enhanced neovascularization compared to non comedo carcinomas (NCCs). Growth fraction determination with Ki-67 antibody showed that 78% of the CCs expressed high proliferating activity compared to 27% of the NCCs. p53 immunoexpression was noted in 78% of the CCs and 20% of the NCCs. Bcl-2 immunoreactivity was observed in 67% of the total cases in 58% of which there was no association with p53 expression. However, an association was found between neovascularization and overexpression of Ki-67 and p53. CONCLUSIONS: This study suggests that neovascularization is an early phenomenon in breast neoplasia and is apparent as early as the in situ stage. CCs express a more aggressive immunophenotype, compared to the other DCIS subtypes, characterized by increased stromal interaction, high proliferating activity, p53 overexpression and a near lack of bcl-2 immunostaining.

Bax protein expression in colorectal cancer: association with p53, bcl-2 and patterns of relapse.

This study evaluated the frequency and the prognostic significance of bax, bcl-2 and p53 proteins in stage B and C adenocarcinomas of the colon and rectum. Paraffin-embedded specimens from 268 patients with colorectal adenocarcinomas, treated with surgery, were assessed; of these 160 cases were Duke's stage B and 108 cases were Duke's stage C disease. Adjuvant chemotherapy was given to all stage C and to 108 out of 160 stage B cancer patients, while those having rectal malignancy also received pelvic radiotherapy. Duke's stage B patients were treated either with surgery alone or with surgery and radiotherapy. The follow-up period at the time of analysis ranged from 12-72 months (median 32 months). Immunohistochemical expression of bax, bcl-2 and mutant p53 proteins was detected with a frequency of 42%, 37% and 48%, respectively. However, the expression was strong only in 17% of tumours, on average. A strong bcl-2 expression was significantly associated with a strong bax expression (p < 0.0001) and with absence of p53 nuclear accumulation (p < 0.005). There was, however, no correlation between bax and p53 proteins. Furthermore, bcl-2 expression was significantly more frequent in grade I and 2 adenocarcinomas compared to grade 3 disease (p = 0.01). In stage B (but not C) adenocarcinomas, bax expression was directly associated with higher risk of local relapse (p = 0.04). By contrast, cases with p53 nuclear accumulation, when they had received adjuvant radiotherapy, were significantly associated with a lower incidence of local relapse (p = 0.01), but a higher rate of distant metastasis (p = 0.06). Multivariate analysis for disease free and overall survival showed that bax expression and high Duke's stage were independent prognostic parameters associated with an unfavourable outcome (p = 0.009 and p = 0.0001, respectively). It was concluded that the immunohistochemical expression of bax is a marker of poor prognosis and of a higher risk of local relapse in patients with colorectal adenocarcinomas. p53 nuclear accumulation is associated with a better local control, following radiotherapy and with a metastatic phenotype. The development of novel monoclonal antibodies recognising specifically the mutated versus the wild type form of proteins would apparently improve the prognostic and predictive value of the immunohistochemically detected apoptotic proteins.

Papillary serous adenocarcinoma of the endocervix: A rare neoplasm. Immunohistochemical profile.

Serous adenocarcinoma of the endocervix is a rare carcinoma similar to the serous carcinoma of the ovary and the endometrium. We report a case of a 63-year-old woman with papillary serous adenocarcinoma arising within the endocervix, describing the clinical presentation and the morphologic characteristics of this rare neoplasm. A detailed immunohistochemical analysis on the expression of low- and high-molecular weight cytokeratins (AE1 and AE3), EMA, CEA, vimentin, B72.3, nm23, estrogen and progesterone receptors, LeuM1 (CD15), p53, Ki-67 antigen, and PCNA by tumor cells has also been carried out, which to our knowledge has not been previously reported.

Tissue imprints in surgical pathology: a rapid intraoperative diagnostic aid.

We studied the intraoperative diagnostic value of imprint cytology in 230 samples obtained from surgical specimens submitted for frozen section diagnosis. A rapid hematoxylin-eosin stain was used. Intraoperative imprint cytology achieved an accuracy rate of 94.3%; for benign lesions the accuracy was 97.5%, and for malignant lesions it was 91%. Overall, the false-negative and suspicious-for-malignancy rates were 1.3% and 4.3%, respectively. No false-positive results were found. The diagnostic yield when intraoperative imprint cytology and frozen section were used together was 99%. It is apparent that imprint cytology is a quick and simple method with wide applicability in the histopathologic diagnosis of lesions from all organs. The value of the method is enhanced when it is used with frozen section diagnosis.

Sources of diagnostic discrepancies in fine-needle aspiration of the breast.

Fine-needle aspiration (FNA) is a valuable technique to use in the evaluation of breast lesions; however, inadequate and discrepant diagnoses do occur. To identify the source and nature of inaccuracies related to the method we studied 39 cases in which FNA posed diagnostic problems. These problems could be attributed to sampling errors (71.8%), to the criteria of adequacy we use at our institution (25.6%), and to interpretation (2.6%). The nature of the breast lesion (68%) was the most common cause of inadequate sampling, followed by the experience of the aspirator (32%).

Diagnosis of thyroid cancer in southwestern Greece.

A prospective study of 1,200 patients with thyroid disease was performed from 1983 to 1988 to appraise the reliability of various diagnostic techniques in patients with thyroid cancer. Histologic confirmation was obtained in 201 patients. By assuming that only solid lesions, single or multiple, represented malignancy, the sensitivity and specificity of ultrasonography was 4.64 and 52.2%, respectively. Findings of fine needle aspiration (FNA) cytology and of carcinoembryonic antigen (CEA) serum concentration were also evaluated. The sensitivity and specificity of these two methods (91.2% and 84.1% for FNA and 89.7% and 81.3% for CEA, respectively) were found to be high enough to permit surgical intervention after a diagnosis of malignancy was made. It appears that the combination of FNA cytology and CEA serum measurement represents the most accurate method for the pre-operative detection of thyroid cancer.

Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix.

Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly-differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis.

Frozen section diagnosis: a quality control study.

In a quality control study we reviewed six hundred and eighty one frozen section specimens sent to our department from 1981 to 1989. Accuracy was 98%. Diagnosis was deferred in 1%. False positive diagnosis for malignancy was made in one (0.15%) case and false negative diagnosis for malignancy in thirteen (2%) cases. Most of the inaccurate diagnoses concerned the female breast and the omentum. Incorrect diagnoses were due to interpretation of the pathologic findings (50%), to microscopic sampling (36%) and to gross sampling (14%). Some of the lesions are difficult to diagnose even in permanent sections. Technical skill and diagnostic expertise are essential for high diagnostic accuracy in the method of frozen section.