The role of pRB, p16 and cyclin D1 in colonic carcinogenesis.

BACKGROUND/AIMS: This study is aimed to investigate abnormal expression of the Rb protein (pRb), p16(INK4a) (p16) and cyclin D1 in colorectal adenomas and adenocarcinomas and to assess the possible alterations in Rb pathway in colorectal carcinogenesis. METHODOLOGY: 44 cases of colorectal adenoma and 44 cases of colorectal adenocarcinoma were examined histopathologically and immunohistochemically using monoclonal antibodies to identify abnormalities of pRb, p16, and cyclin D1 expression. Staining degree of above-mentioned markers was assessed by using a semi-quantitative method in all cases in order to determine any staining differences. RESULTS: In 70.5% of the adenomas and 97.7% of the adenocarcinomas, an overexpression of pRb was found. There was a statistically significant relationship between the immunoreactivity of pRb and villous/tubulovillous types of adenomas (p < 0.05). There was a loss of p16 expression in 84.1% of adenomas and 61.4% of adenocarcinomas. Statistically significantly, the p16 overexpression was not seen in any of tubular adenomas (p < 0.001). Overexpression of cyclin D1 was found in only 9.1% of adenomas, while 31.8% of adenocarcinomas overexpressed this protein. Loss of expression of cyclin D1 was similar in adenomas and adenocarcinomas (27.3% and 25%, respectively). Staining degrees of all three cell cycle proteins were shown to be statistically different in adenomas and adenocarcinomas, for pRb (p = 0.001), for p16 ( p = 0.045), and cyclin D1 ( p = 0.05). Also, there was only a mild agreement with respect to p16 and cyclin D1 relationship between for adenomas ( K = +0.28 p = 0.051) and for adenocarcinomas ( K = +0.35 p = 0.017). Besides, there was no correlation between the expression of pRb, p16, and cyclin D1 and clinicopathological tumor characteristics and prognostic data such as stage or lymph node/liver metastasis. CONCLUSIONS: pRb, p16 and cyclin D1 are shown to be aberrantly expressed in both colorectal adenomas and adenocarcinomas. It can be claimed that disturbances in Rb pathway take part in colonic carcinogenesis and pRb, p16 and cyclin D1 play an ever increasing role in the further stages of adenoma-carcinoma sequence.

Can CD10 be used as a diagnostic marker in thyroid pathology?

CD10-common acute lymphoblastic leukemia antigen is a membrane-bound zinc metalloproteinase that is expressed by different hematopoietic cell types at unique stages of lymphoid and myeloid differentiation. It was reported to be expressed in various nonlymphoid cells and tissue, as well as in various types of neoplasms. Recently, it has been found to be useful in the differential diagnosis of benign and malignant follicular-patterned lesions of the thyroid. In the present study, we evaluated the staining pattern of CD10 in various thyroid lesions, including 14 benign and 61 malignant cases, as well as in adjacent thyroid tissue. CD10 was negative in normal thyroid tissue, adenomatous nodules, minimally invasive follicular carcinoma, and well-differentiated carcinoma. It was expressed in nine of 14 (64.2%) conventional papillary carcinomas, four of 24 (16.6%) follicular variant of papillary carcinomas, three of six (50%) papillary microcarcinomas, one of nine (11.1%) widely invasive follicular carcinomas, and three of ten (30%) follicular adenomas. In contrast to results of previous studies, CD10 is not useful in the classification of thyroid follicular lesions as benign or malignant, but it shows strong positivity in conventional papillary carcinoma.

The significance of venous dominance in color Doppler ultrasound for the diagnosis of primary nodular skin lesions: a new perspective in classification.

The aim of this study was to investigate the significance of color Doppler ultrasound (CDUS) findings in the differential diagnosis of suspicious nodular skin lesions and to compare the results according to the Giovagnorio 1999 classification and the modified classification. Forty nodular skin lesions were evaluated with CDUS and US. The number of arteries and veins was recorded in hypervascular lesions. Findings were compared with histopathological results. The specificity and predictivity of the modified classification were higher than those of the Giovagnorio 1999 classification.

Comparison of the nuclear matrix protein 22 with voided urine cytology in the diagnosis of transitional cell carcinoma of the bladder.

Several urinary markers for transitional cell carcinoma have been investigated, including urine cytology, bladder tumor antigen, autocrine motility factor receptor and fibrin degradation products. Unfortunately, they have poor overall sensitivity. The United States Food and Drug Administration have recently approved nuclear matrix protein (NMP 22) for the detection of occult or rapidly recurring disease after transurethral resection of bladder tumor. The objective of the current study was to assess the sensitivity of NMP 22 for the detection of bladder carcinoma, as well as to correlate the NMP 22 values with multiplicity of tumor, tumor size, configuration, stage and grade respectively. A total of 78 patients (38 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of urine cytology and NMP 22. Comparative results demonstrate a clear superiority of NMP 22 in bladder cancer detection (52.6% vs 31.6% sensitivity), while specificity was in favor of urine cytology (100% vs 82.5%). For superficial tumors, sensitivity was 78.5% for NMP 22 and 41.6% for cytology and for invasive cancers, sensitivity was 90% for NMP 22 and 60% for cytology. Urinary NMP 22 levels were significantly correlated with tumor grade and were significantly higher in large tumors than small tumors. NMP 22 test results showed sufficient sensitivity in comparison with urine cytology for the detection of transitional cell carcinoma. However, we do not think that it is a useful tool as a substitute for endoscopic examination for the detection and surveillance in bladder cancer.

Features of chronic inflammation at the gastric cardia and the relationship with Helicobacter pylori infection and oesophagitis.

BACKGROUND: The etiopathogenesis of chronic inflammation at the gastric cardia is still debated. It is suggested that carditis may be a finding of gastro-oesophageal reflux disease (GORD) or it may occur as a result of the gastritis caused by Helicobacter pylori (H. pylori) infection. AIM: To examine morphological features of carditis, as well as the associations of carditis with Helicobacter pylori gastritis and oesophagitis as a marker of gastro-oesophageal reflux disease. PATIENTS AND METHODS: Endoscopic biopsy specimens obtained systematically from oesophagus, cardia, corpus and antrum of 135 dyspeptic patients were retrospectively evaluated. In biopsies, we have searched for any correlations between clinical, endoscopic, and histological features. RESULTS: Carditis was detected in 123 (91.1%) of the cases. The mean age of the carditis group was 47.9 years and the male-to-female ratio was 1.08:1. The relation of carditis with age and sex was not significant (p = 0.19 and p = 0.24, respectively). All cases of the carditis group had concomitant chronic gastritis. In these cases, chronic inflammation, degree of neutrophil-mediated activity and H. pylori colonisation were significantly correlated in cardia, corpus and antrum (p < 0.001). Intestinal metaplasia was observed in 14 cases (11.3%) and, was associated with H. pylori colonisation (p < 0.001). Microscopic oesophagitis detected in 37.7% cases also showed correlation with reflux symptoms and endoscopic oesophagitis but not carditis. When all cases with carditis were evaluated for H. pylori infection and oesophagitis, which are presumed risk factors for carditis, H. pylori infection appeared to be an independent risk factor for carditis (p = 0.012), while oesophagitis did not. CONCLUSIONS: This study suggests that carditis is commonly found in patients presenting with dyspepsia and the histological features of carditis were similar to those seen in H. pylori gastritis in antrum and corpus. In addition, our data have also shown that carditis was significantly associated with H. pylori infection but not with symptoms or signs of GORD.

Inguinal keratotic Basal cell carcinoma mimicking giant solitary trichoepithelioma.

Keratotic basal cell carcinoma may not only clinically but also histologically share more or less the same features with giant solitary trichoepithelioma. It can be difficult to distinguish these two entities from each other, even for an experienced dermatopathologist. We present an unusual case of inguinal keratotic basal cell carcinoma mimicking giant solitary trichoepithelioma in a 56-year-old woman with a finger-like tumor of 20 years duration. The patient presented with an asymptomatic, skin colored, firm, nonulcerative, nodular lesion. Scanty mitotic activity and apoptotic cells were the histopathologic findings against basal cell carcinoma, whereas absence of papillary mesenchymal bodies, presence of peritumoral lacunae detected only around the solid areas, and accumulation of amyloid-like hyalinized material were the findings in favor of basal cell carcinoma. This case illustrates that keratotic basal cell carcinoma must be taken into account in the differential diagnosis of inguinally located solitary, polypoid masses, especially giant solitary trichoepithelioma.

Combination thymosin-alpha 1 and interferon-alpha 2b in the treatment of anti-HBe-positive chronic hepatitis B in Turkey.

BACKGROUND/AIMS: The most prevalent type of chronic hepatitis B in Turkey is anti-HBe-positive. No consistently effective therapy is yet available for the treatment of these patients. The aim of this study was to assess the efficacy and safety of interferon-alpha and thymosin-alpha 1 combination in the treatment of naive anti-HBe-positive and HBV DNA-positive chronic hepatitis B patients. METHODOLOGY: Twenty-one patients were enrolled in the study. All patients had documented anti-HBe-positive, HBV DNA-positive chronic active hepatitis B without evidence of cirrhosis. Patients received a 26-week combination course of 1.6 mg thymosin-alpha 1 subcutaneously twice a week and 10 MIU interferon-alpha subcutaneously three times a week, followed by interferon-alpha monotherapy at the same dose for another 26 weeks. After treatment patients were observed for a further 26 weeks. Endpoints were a normalization of alanine aminotransferase and negativity of HBV DNA at weeks 52 and 78, as well as an improvement in liver histology at week 78. RESULTS: Eighteen (87.7%) of the 21 patients responded by losing serum HBV DNA and normalizing alanine aminotransferase values at the end of the 52-week treatment period. Sixteen (76.2%) of these patients became sustained responders, with normal alanine aminotransferase and negative HBV DNA at the end of 78 weeks. Two patients were non-responders, two relapsed and one had a breakthrough during therapy. Significant improvements in the Knodell histological activity index were observed in the responders. No adverse events other than those seen previously with interferon monotherapy were reported. CONCLUSIONS: Combination interferon-alpha 2b and thymosin-alpha 1 treatment may provide a safe and effective therapeutic approach for the difficult-to-treat anti-HBe-positive chronic hepatitis B patients. Further controlled studies are needed to assess the full role of this treatment strategy.

Histological and clinical predictive value of determination of tissue CagA status by PCR in Helicobacter pylori infected patients; results of the large population based study in western Turkey.

BACKGROUND/AIMS: Early experimental and epidemiological studies have suggested that the presence of cagA gene was a virulence factor for Helicobacter pylori. We aimed to investigate the clinical significance of tissue CagA status in Helicobacter pylori infected patients and to assess its association with histological changes in gastric mucosa. METHODOLOGY: Three hundred and forty-five patients with Helicobacter pylori infection established by both urease test and histological examination were included in the study. The symptoms of the patients were recorded according to the Glasgow dyspepsia scale. Biopsies (cardia, corpus, angulus and antrum) were evaluated histologically according to the Sidney system. The cagA status was determined by polymerase chain reaction method from an antral biopsy. Polymerase chain reaction studies were performed by Wizard genomic DNA purification system (promega). We also determined the serum levels of tumor necrosis factor-alpha, and gastrin. They were all prescribed lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxycillin (1 g b.i.d.) for a week. At the 8th week a second endoscopy was performed and further biopsy specimens were obtained from the same sites. Mann-Whitney U and chi 2 tests were used for statistical analyses. RESULTS: Two hundred and thirty-five patients (68.1%) were infected with cagA-positive strains of Helicobacter pylori and the other 110 patients (31.8%) were infected with cagA-negative strains. We compared the parameters and measurements studied in this trial between the patients infected with cagA-positive and negative Helicobacter pylori strains. Helicobacter pylori density was greater in the cagA-positive group by 1.9 +/- 0.9 than in the cagA-negative group by 1.2 +/- 0.7 (P = 0.01). Helicobacter pylori activity and chronic inflammation also were significantly higher in the cagA-positive group with the values of 1.4 +/- 0.8 and 2.1 +/- 1.1 than in the cagA-negative group with 0.7 +/- 0.2 and 1.3 +/- 0.5, respectively (P = 0.001, P = 0.002). The presence of atrophy and lymphoid aggregate was not different between the two groups (P > 0.05). However intestinal metaplasia was shown to be significantly frequent in patients infected with cagA-positive Helicobacter pylori strains (0.001). Serum tumor necrosis factor-alpha and gastrin levels which were accepted as the markers of inflammation in Helicobacter pylori infection were increased in the cagA-positive group compared with the cagA-negative group. Serum tumor necrosis factor-alpha level was 11.3 +/- 7.0 pg/mL in the cagA-positive group and 4.9 +/- 2.7 pg/mL in the cagA-negative group (P = 0.001). Gastrin level also showed a significant difference between two groups by 66.8 +/- 31.1 pg/mL and 37.2 +/- 19.2 pg/mL, respectively, in the cagA-positive and negative groups (P = 0.001). The virulent strains seem to cause peptic ulcer more frequently. Peptic ulcer was determined in 17% of patients in the cagA-positive group but this ratio was 9% in the cagA-negative group (P = 0.608). Although, all these differences of the degree of inflammation, clinical spectrum and biochemical parameters were seen, interestingly there was no significant difference in the severity of the symptoms of the patients in both groups according to Glasgow dyspepsia severity score (P = 0.20). CONCLUSIONS: Our results confirm that cagA-positive strains of Helicobacter pylori cause greater histological changes. However this virulence is not associated with more severe symptoms. The histological changes can be predictable by determining the tissue cagA status.