Comparing subjective and digital image analysis HER2/neu expression scores with conventional and modified FISH scores in breast cancer.

BACKGROUND: HER2/neu expression and fluorescence in situ hybridisation (FISH) amplification have therapeutic significance. AIMS: To compare subjective HER2/neu expression scores with digital image analysis (DIA) and conventional and modified FISH scores in breast cancer. METHODS: Sixty HercepTest-immunostained breast carcinomas, prospectively scored as consensus 2+ and 3+ (DAKO protocol) by two observers, were analysed with DIA, and conventional (Vysis) and modified FISH scoring protocols. RESULTS: With consensus scoring, 23 (38%) of the 60 cases were 2+ and 37 (62%) were 3+. Agreement with DIA scores was 100%. With conventional FISH scoring, 4 of the 3+ cases did not show amplification, but all of those negative cases had high HER2/neu copy numbers. With the modified FISH scoring protocol, all HercepTest immunohistochemical 3+ cases were amplified. Of the 2+ cases, 3 were amplified with the modified FISH protocol and 4 with the conventional FISH protocol. CONCLUSIONS: Modified FISH scores were better correlated with HercepTest 3+ consensus and DIA scores than were conventional FISH scores. HER2/neu DIA scoring is a cost-effective supplementary tool in surgical pathology.

Proliferation markers and DNA content analysis in urinary bladder TaT1 urothelial cell carcinomas: identification of subgroups with low and high stage progression risks.

AIMS: To evaluate whether in situ biomarkers Ki67, mitotic activity index (MAI), p53, mean area of the 10 largest nuclei (MNA10), and whole genome DNA ploidy by flow and image cytometry (FCM and ICM, respectively) have independent prognostic value in urinary bladder urothelial cell carcinomas (UCs). METHODS: Ki67 and p53 immunoquantitation was performed in TaT1 consensus diagnosis UCs. MAI and MNA10 were also determined. Single cell suspensions were stained (DAPI for FCM; Feulgen for ICM). There was enough material for all measurements in 171 cases. Kaplan-Meier curves and multivariate survival analysis (Cox) were used to assess the prognostic value of all features (including classic clinicopathological risk factors, such as stage, grade, multicentricity, carcinoma in situ). RESULTS: Thirteen (7.6%) patients progressed. Of the classic factors, grade was strongly prognostic in univariate analysis, as were all the biomarkers. In multivariate analysis, the strongest independent combinations for progression were MNA10 (threshold (T) = 170.0 micro m(2)) plus MAI (T = 30), or MNA10 (T = 170.0 micro m(2)) plus Ki67(T = 25.0%). p53 (T = 35.2%) plus Ki67 (T = 25.0%) also predicted progression well, with high hazard ratios, but p53 measurements were not as reproducible as the other features. The prognostic value of the quantitative biomarkers exceeded that of the classic risk factors and DNA ploidy. The sensitivity, specificity, positive, and negative predictive values of MNA10/MAI or MNA10/Ki67 at the thresholds mentioned were 100%, 79%, 57%, and 100%, respectively. These feature combinations were also strongest prognostically in the high risk treatment subgroup. CONCLUSIONS: The combined biomarkers MNA10/Ki67 or MNA10/MAI are more accurate and reproducible predictors of stage progression in TaT1 UCs than classic prognostic risk factors and DNA ploidy.

Incidence of acute nonperforated and perforated appendicitis: age-specific and sex-specific analysis.

This prospective study was performed to investigate epidemiological characteristics in terms of the age- and sex-specific incidence in patients with perforated and nonperforated appendicitis. The study population comprised 1486 consecutive patients who underwent appendectomy for suspected acute appendicitis between 1989 and 1993. Two patient cohorts [n = 544 (37%)] were analyzed with regard to prehospitalization duration of symptoms and in-hospital observation time. The crude incidence of acute appendicitis was 86 per 100,000 per year. Although the incidence of nonperforated appendicitis was highest among adolescents and young adults (13-40 years of age), perforated appendicitis occurred at almost the same incidence in all sex and age groups. The diagnostic accuracy was 76%. Perforated appendicitis occurred in 19%, with higher rates in small children and the elderly, irrespective of gender. A high diagnostic accuracy was not associated with an increased rate of perforation. In small children and the elderly, the diagnostic accuracy was low and the perforation rate high. Patients with perforation had a significantly longer duration of symptoms as well as in-hospital observation time than did patients with nonperforated appendicitis. Perforated appendicitis showed a different incidence pattern than nonperforated appendicitis and was associated with a significantly longer duration of symptoms and in-hospital observation time, probably due to patient-related factors. We suggest this observation deserves attention regarding clinical diagnosis and treatment decision-making for patients with suspected acute appendicitis.

A prospective study of the length of the distal margin after low anterior resection for rectal cancer.

The length of distal margin between the lower border of the tumour and the level of division during low anterior resection may be related to the rate of local recurrence. The method of measuring the distal clearance is not usually stated in reports of the operation. The distal margin was measured prospectively in 5 different ways in 20 patients. A difference was observed between various methods of measurement of the same specimen in situ, unpinned and pinned out before and after fixation. The margin was significantly less (p less than 0.001) in unpinned compared with pinned specimens. There was poor correlation between the in situ measurement and that determined by the pathologist in both unpinned and pinned specimens. There was no significant difference before and after fixation if the specimen had been pinned but significant (p less than 0.001) shrinkage occurred with fixation when the specimen had not been pinned.

Pleomorphic adenoma of the human breast with local recurrence.

Pleomorphic adenoma of the human breast is a rare, benign tumor for which the literature is sparse. A local recurrence has been reported only once before. The diagnostic challenge of this cancer-imitating lesion is emphasized in this report. Although local excision of the tumor is the treatment of choice, almost 50% of the patients reported have undergone fairly extensive surgery, i.e., simple or radical mastectomy. A paraffin secretion of the excised tumor is mandatory to confirm the benign nature of the lesion to avoid an unnecessary mastectomy for a benign condition.