M. Hossein Saboorian

Ethnic Differences in the Prevalence of Cryptogenic Cirrhosis

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) associated with obesity and type 2 diabetes mellitus (DM) is postulated to be the cause of most cases of cryptogenic cirrhosis (CC). While ethnic differences in the prevalence of obesity and DM in the United States are well documented, there is little information regarding prevalence of CC or NASH among different U.S. ethnic groups. This study was performed to assess the demographic characteristics of patients with CC at a U.S. county hospital with a racially and ethnically diverse patient population.METHODS:Medical records and pathology databases were reviewed to identify patients at Parkland Memorial Hospital, Dallas County, Texas from 1990 to 2001 with CC or cirrhosis attributed to NASH.RESULTS:Forty-one patients (12 men, 29 women) were found to meet these criteria. Of these, 68% were obese (BMI ≥ 30) and/or had type 2 DM and 74% of liver biopsies revealed one or more features of NASH. Of patients with CC 68% were Hispanic while only 7% were African American, despite the fact that Hispanics comprised <26% and African Americans >40% of adult medicine patients. Prevalence of CC among Hispanic and African American patients was 3.1-fold higher and 3.9-fold lower, respectively, than among European American patients despite similar prevalence of DM among Hispanics and African Americans.CONCLUSIONS:These findings support the hypothesis that NASH associated with obesity and DM is responsible for the majority of cases of CC among Hispanics and European Americans. However, the current findings also indicate that this form of cirrhosis is unexpectedly rare among African Americans.

Survivin expression is associated with features of biologically aggressive prostate carcinoma

Survivin counteracts cell death and controls mitotic progression. The objectives of the current study were to compare the expression patterns of survivin in normal prostate, primary prostate carcinoma, and lymph node tissues involved with prostate carcinoma and to determine whether the expression of survivin is associated with prostate carcinoma characteristics and progression.

The current spectrum of gastric polyps: a 1-year national study of over 120,000 patients.

OBJECTIVES:To use a large pathology database (Caris Diagnostics) to analyze the frequency and associations of gastric polyps in a nationwide US population.METHODS:A total of 121,564 esophagogastroduodenoscopy (EGD) procedures from private practices in 36 states in the Caris Diagnostics database from 1 April 2007 to 31 March 2008 were searched for the endoscopic designations of polyp, nodule, and mass, and for the pathological diagnoses that commonly present as gastric polyps. Pertinent demographic data, clinical indications for EGD, and information regarding Helicobacter pylori infection, reactive gastropathy, chronic inactive gastritis, and intestinal metaplasia were also obtained.RESULTS:A total of 78,909 of the 121,564 patients who underwent EGD had gastric biopsies. The prevalence of gastric polyps in the EGD population was 6.35%; 77% were fundic gland polyps, 17% hyperplastic polyps/polypoid foveolar hyperplasia, 0.69% adenomas, and 0.1% inflammatory fibroid polyps. Malignant neoplasms were slightly >2%. None of the benign gastric polyps had a significant positive association with concurrent H. pylori infection; intestinal metaplasia was detected in the background of 52.2% of carcinoids, 29.6% of adenomas, 20.1% of xanthomas, and 13% of adenocarcinomas and hyperplastic polyps. Adenomas were rarely associated with synchronous adenocarcinomas.CONCLUSIONS:The relative prevalence of fundic gland polyps in this population was much higher than that reported earlier, most likely because of the widespread use of proton pump inhibitors. H. pylori- and atrophy-associated polyps, including adenomas, were less common than in earlier series.

Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard.

This retrospective study of formalin-fixed infiltrating breast cancer specimens compared manual immunohistochemical assay with a new image analyzer-assisted immunohistochemical quantitation method, using fluorescence in situ hybridization assay (FISH) as the standard. Following the manual immunohistochemical assay, 189 cases, including most manual immunohistochemically positive and some random negative cases, were analyzed by FISH assay for Her-2/neu gene amplification and by the Automated Cellular Imaging System (ACIS) for immunohistochemical staining. Using the FISH standard, the ACIS immunohistochemical assay attained a higher concordance rate and sensitivity than the manual immunohistochemical assay (91.0% and 88% vs 85.7% and 71%, respectively), with only a slight decrease in specificity (93% vs 96%, respectively). In particular, the ACIS immunohistochemical assay resulted in a higher correlation with the FISH assay in the manual immunohistochemical assay 2+ cases. The ACIS immunohistochemical assay achieved higher accuracy than the manual method according to receiver operating characteristic curve analysis. The ACIS method represents a substantial improvement over the manual method for objective evaluation of the HER-2/neu status.

Aneusomy 17 in Breast Cancer: Its Role in HER-2/neu Protein Expression and Implication for Clinical Assessment of HER-2/neu Status

HER-2/neu protein overexpression in breast cancer is mostly caused by HER-2/neu gene amplification. However, it is unclear whether aneusomy 17 may also play a role. Using immunohistochemistry assay (IHC) with DAKO antibody and manual quantitation, 189 specimens were selected from archival invasive breast cancer specimens, including most IHC-positive and some IHC-negative cases (n = 158 and 31, respectively). They were then analyzed by PathVysion fluorescence in situ hybridization (FISH) assay (Vysis, Inc., Downers Grove, IL) and by an image analyzer (ACIS; ChromaVision Medical Systems, Inc., San Juan Capistrano, CA)–assisted IHC quantitation. Ninety-two cases contained disomy 17 (chromosome 17 centromere, 1.76–2.25 signals per cell) whereas 97 cases had aneusomy 17, including 82 with low polysomy (2.26–3.75 signals per cell), 10 with high polysomy (≥3.76 signals per cell), and 5 with hypodisomy (≤1.75 signals per cell). HER-2/neu protein expression had the highest correlation with HER-2/neu gene dosage (copy number; r = .826), followed by the HER-2/neu gene to chromosome 17 ratio (r = .733). The lowest correlation was with the chromosome 17 copy number (r = .307), on which the 10 cases with high polysomy 17 had a disproportionately high impact. The FISH assay using the PathVysion criterion for HER-2/neu gene amplification (HER-2/neu gene to chromosome 17 ratio, ≥2.00) achieved higher concordance with ACIS IHC than did an alternative FISH criterion (absolute HER-2/neu gene copy number, ≥4.00 signals per cell). Most ACIS IHC-PathVysion FISH–discordant cases contained disomy or low polysomy 17, whereas all 10 cases with high polysomy 17 had no such discordance. However, two cases with monosomy 17 had ACIS IHC-PathVysion FISH discordance, i.e., with gene amplification, but no protein overexpression. Both cases would have had no gene amplification if the alternative FISH criterion had been used. In conclusion, aneusomy 17 is common in breast cancer. Except in a certain subset of cases, aneusomy 17 probably is not a significant factor for HER-2/neu protein expression or for clinical assessment of HER-2/neu status.

ThinPrep Pap Test

OBJECTIVE Although the ThinPrep Pap Test is replacing conventional Pap smears in many clinical practices, experience with the identification of glandular lesions is limited. In this study, ThinPrep cytology of glandular lesions was evaluated in a large, inner city teaching hospital with high rates of glandular abnormality. STUDY DESIGN Six months of ThinPrep diagnoses in 1998, following nearly 100% conversion of the laboratory to the ThinPrep Pap Test, were compared to January-December 1997 conventional smear diagnoses for glandular disease. Biopsy confirmation was evaluated for these cases. Findings on all biopsy-confirmed glandular cases were also compared to findings on cytology. RESULTS Similar overall rates of glandular cytology were found. For conventional smears (12 months), 46 cases were diagnosed out of 43,289 smears (0.11%). For ThinPrep cytology (six months), 36 cases were diagnosed out of 25,783 slides (0.14%, P = NS). In the year 1997, 9 biopsy-confirmed conventional smear diagnoses of adenocarcinoma in situ (AIS) or adenocarcinoma were noted versus 10 for six months of 1998 for the ThinPrep method. A statistically significant reduction in the number of miscellaneous nonglandular (squamous) biopsy diagnoses were found with ThinPrep glandular cytology (14 vs. 4 cases, P < .05). For known biopsy-confirmed glandular cases of AIS or adenocarcinoma, a statistically significant reduction in the cytology false negative rate was noted with the ThinPrep method (17 vs. 4 cases, P < .02). CONCLUSION The ThinPrep method provides more accurate diagnoses of glandular disease, with an increase in both sensitivity and specificity for glandular lesions.

Promoter hypermethylation profile of ovarian epithelial neoplasms

Purpose: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Experimental Design: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARβ, E-cadherin,H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. Results: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13%) and E-cadherin (13%). LMP tumors also showed p16 (22%) and E-cadherin (17%) methylation, in addition to RARβ (9%) and H-cadherin (4%). All eight genes were hypermethylated in invasive cancers at a frequency of 9% to 30%. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78% versus 44% (LMP; P = 0.03) and 26% (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSF1A (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003). Conclusions: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.

ThinPrep Detection of Cervical and Endometrial Adenocarcinoma A Retrospective Cohort Study

The current study was performed to compare the accuracy of the ThinPrep™ Papanicoloau (Pap) test with that of the conventionally prepared Pap smear in detecting cervical and endometrial adenocarcinomas.

Nephrectomy after radiofrequency ablation-induced ureteropelvic junction obstruction: potential complication and long-term assessment of ablation adequacy

Little information is available concerning the morbidity of radiofrequency ablation (RFA) or the evolution of an RFA lesion over time. We report our findings in a kidney removed 1 year after RFA of a 2.3-cm renal tumor. After RFA, the patient experienced flank pain, followed by hydronephrosis, ureteropelvic junction obstruction, and eventual loss of function in the treated kidney. Nephrectomy revealed no residual renal cell carcinoma. RFA can completely destroy renal cell carcinoma in situ without histologic evidence of persistence or recurrence for up to 1 year after treatment. Care must be taken to avoid concurrent damage to the collecting system.

Diagnostic utility of the HepPar1 antibody to differentiate hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration samples.

The cytopathologic distinction between hepatocellular carcinoma (HCC) and metastatic carcinoma (MC) in the liver can be problematic, especially in patients with poorly differentiated HCC, in whom a trabecular pattern, bile production, and Mallory bodies may not be apparent on small fine‐needle aspiration (FNA) samples. HepPar1 (OCH1E5) is a monoclonal antibody specifically developed to react with hepatocytes. It rarely reacts with bile duct and nonparenchymal liver cells.