Biomedical subjects

Jan P Baak

Publications and source records attributed to Jan P Baak.

3 recordsLinked to original sources

PubMed2005

The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system.

BACKGROUND: The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS: A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had < 1 year of follow-up. RESULTS: Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with < 1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS: The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.

Adult↗

PubMed2004

Evaluation of prospective, routine application of Ki-67 immunoquantitation in early CIN for assessment of short-term progression risk.

OBJECTIVE: To prospectively validate, in early cervical intraepithelial neoplasia (CIN), routine assessment of a previously developed prognostic Ki-67 immunoquantitative progression-risk model. STUDY DESIGN: Two hundred sixty-six consecutive cervical biopsies taken for an abnormal cytologic smear were routinely diagnosed by experienced pathologists as CIN. Ki-67 immunoquantitation was performed routinely by 3 technicians blinded to clinical and pathologic information. Progression of CIN 1-2 to CIN 3 in histologic follow-up biopsies was used as the intermediate end point. RESULTS: In 58 (22%) biopsies, technical shortcomings prevented Ki-67 immunoquantitation, and in 22 biopsies no follow-up was available. The routine diagnosis in the 186 remaining biopsies was CIN 1 = 24, CIN 2 = 56 and CIN 3 = 106. In 52 marker biopsies with expert review diagnosis of CIN 1-2 and adequate follow-up, histologic biopsies revealed CIN 3 in 9 (17%) cases: 9 of 34 (26%) of Ki-67 high-risk and 0 of 18 (0%) of Ki-67 low-risk lesions (log rank = 5.0, P = .03). Routine CIN grade (1 or 2) was not prognostic (P = .65). Eleven (55%) of 20 CIN 1 and 7 of 32 (22%) CIN 2 cases were Ki-67 low risk and none progressed, contrasting with 4 of 9 (44%) progressions of Ki-67 high risk CIN 1s and 5 of 25 (20%) high risk CIN 2s. Expert CIN grades were stronger prognostically than routine CIN grade, but Ki-67 was still stronger. CONCLUSION: Routine Ki-67 immunoquantitative progression prediction in CIN 1-2 is more predictive of CIN 3 in follow-up than are routine and review CIN grades.

Biopsy↗

PubMed2003

Reproducibility and prognostic variability of grade and lamina propria invasion in stages Ta, T1 urothelial carcinoma of the bladder.

PURPOSE: We assessed the reproducibility and prognostic variability of grade and lamina propria invasion in stages Ta, T1 urothelial carcinoma of the bladder. MATERIALS AND METHODS: A total of 130 consecutive stages Ta, T1 urothelial carcinomas routinely diagnosed by 15 pathologists (original diagnosis) were reviewed by 3 independent experienced pathologists using 1999 WHO criteria (diagnoses 1 to 3 and reviewer consensus diagnosis). Interreviewer disagreement cases were blindly reviewed again. Each remaining disagreement case was discussed in a multihead microscope session to attempt to solve remaining disagreements. In cases of continuing disagreement the majority diagnosis on stage and grade was considered the consensus diagnosis. Stage progression at followup was the dependent variable. Stage progression-free Kaplan-Meier survival curves and hazard ratios of each stage and grade diagnosis were calculated and prognostic variability was determined. RESULTS: There was complete interobserver agreement on stage and grade among reviewers in 80% and 59% of cases, while it was 87.7% and 75.4%, respectively, after the second review. More than 1 grade difference occurred in 1.5% of cases (0% after the second review). The consensus and original diagnoses agreed on stage and grade in 68.5% and 62.3% of cases, respectively. Assignment of individual cases to 1 category of the 1999 WHO classification per reviewer varied considerably. The incidence of cases classified as stage T1 grade 3 by the reviewers was between 12.3% and 18.9% (average 14.1%). Consensus diagnosis grade had the strongest prognostic value (HR 68.8, range 8.9 to 528.0). Of the 63 original diagnoses of stage T1 tumors the consensus diagnosis down staged 35 (55.6%) to Ta and up staged 8 (12.7%) to T2-3. Progression was more common in the 20 consensus diagnosis stage T1 cases (5 or 25%) than in the 55 original diagnosis stage T1 cases (11 or 20%). Original diagnosis stage T1 tumors that were down staged by the consensus diagnosis showed less progression than consensus diagnosis confirmed stage T1 tumors (17% versus 25%). The prognostically worst subgroup (T1 grade 3) also showed considerable prognostic variation among reviewers (28% to 76% at 5 years of followup), in that the consensus diagnosis again had the highest prognostic significance (HR 3.5, range 1.2 to 10.2). At the end of the study all pathologists expressed that they were regularly uncertain about stage and grade assessment in an individual case in a considerable percent of all cases. CONCLUSIONS: Observer prognostic variability in staging and grading is considerable with potentially strong implications for patients. Interobserver variation did not decrease using the new 1999 WHO grading classification.

Carcinoma, Transitional Cell↗