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Jan P A Baak

Publications and source records attributed to Jan P A Baak.

At least 19 recordsLinked to original sources
PubMed2006

The prognostic value of proliferation in lymph-node-negative breast cancer patients is age dependent.

In lymph-node-negative invasive breast cancer patients<55 years, the proliferation marker mitotic activity index (MAI) has previously been shown to be the strongest prognosticator. In studies without age definition, MAI was not strongly prognostic. We investigated the age dependency of the prognostic value of proliferation for distant metastasis-free (MFS) and overall cancer-related survival (OS) in 1004 histologically diagnosed T1-3N0M0 invasive breast cancers (n=516, <55 years; n=322, 55-70 years; n=166, >70 years) without systemic adjuvant therapy and long follow-up (median: 108 months). The MAI decreases with age and the prognostic value of MAI varied by age group. For patients<55 years, hazard ratios (HR) for MAI>or=10 versus<10 for MFS and OS were 3.1 and 4.4, respectively (P<.0001 for both), but only 1.9 and 1.9 (P=.004 and .006) for patients aged 55-70 years, while over 70 years, MAI was not significant (P=.11). The prognostic value of proliferation was age-dependent. Prognostic breast cancer studies must clearly indicate the age group being studied.

Adult↗
PubMed2006

A monotonous population of elongated cells (MPECs) in colorectal adenoma indicates a high risk of metachronous cancer.

Accurate predictors for metachronous colorectal cancer (CRC) development after polypectomy are lacking. We evaluated the prognostic value of classical clinicopathologic features and a monotonous population of elongated cells (MPECs) in colorectal adenomas from 171 consecutively selected population-based patients with long-term follow-up. Quantitative image analysis, and univariate and multivariate regression analysis were applied. Ten of 171 adenomas (5.8%) developed metachronous CRC (defined as >24 mo interval and >5 cm from the index adenoma to the cancer). Median follow-up of adenomas with metachronous CRC was 68.4 and without cancer 149.7 months (range: 25 to 192 and 25 to 256, respectively). The most prognostic classical features were the localization of the marker adenoma as proximal (ie, in the cecum through transverse colon) versus distal from the transverse colon [P=0.0003, hazard ratio (HR)=8] and the number of polyps found during colonoscopy ( 2, P=0.002, HR=6). Quantitative features of the MPECs included the longest nuclear axis and variance of the number of nuclei with 2 neighbors (higher and lower in cancer cases, respectively). Of the 171 adenomas, 50 (29%) had MPECs, of which 9 (18%) patients developed metachronous CRC at follow-up, contrasting 1/121 (0.8%) without MPECs (P=0.0003, HR=23). MPECs occurred in both low-grade and high-grade dysplasia, and in tubular and (tubulo) villous adenomas. MPECs had the strongest predictive value for metachronous CRC development. Adenomas proximally located had additional value but only if they were MPEC positive (which only occurred in 5 adenomas, 3 of which (60%) developed cancer). Having more than 2 polyps also had additional prognostic value but only in MPEC-negative adenomas [10 cases; 1 (10%) developed cancer]. Dysplasia grade and histologic growth pattern had no additional value. Thus, colorectal adenomas with subsequent metachronous cancer development can be identified more accurately with MPECs than with classical prognostic factors.

Adenoma↗
PubMed2006

Success predictors of adjuvant chemotherapy in node-negative breast cancer patients under 55 years.

BACKGROUND: Adjuvant systemic chemotherapy (ASCT) in lymph node-negative breast (LN-) cancers improves survival. The majority of (LN-) patients receive ASCT when the St. Gallen criteria or its modifications are used, as accurate identifiers which patients benefit from ASCT are lacking. This may imply over-treatment in many patients. AIM: To evaluate which patients or primary tumor factors predict ASCT success. MATERIAL AND METHOD: Retrospective analysis by single and multivariate survival analysis of clinical and tumor characteristics in (LN-) breast cancers <55 years, related to ASCT (n=125) or-not (n=516). RESULTS: The two patient groups did not differ in age, tumor diameter, grade, type, number of mitoses and other factors. Fourteen-year survival for the ASCT and non-ASCT patients was 83% and 74% (Hazard Ratio=HR=0.33; p<0.0001, 9% absolute=12% relative difference). Subgroup analysis showed that the recurrence-free survival=RFS of ASCT treated vs. non-treated patients differed in patients with grade 1 cancers (p=0.008), grade 2 cancers (p=0.004), grades 3 (p=0.02), tumors under and >or=2 cm (p=0.001 and 0.0002), oestrogen receptor-positive or -negative tumors (p=0.003,0.04), MAI < 10 and >or=10 (p=0.005,0.003) and fibrotic focus absent (p=0.002). With multivariate analysis the most important predictor of ASCT effect was the MAI. In patients with slowly proliferating tumors (MAI <3) no advantage was found between patients treated-or-not with adjuvant chemotherapy (RFS=92% and 91%, p=0.13, p=0.63 for overall survival), contrasting those with MAI >or=3 (p=0.0001; HR=0.32, 95% CI 0.18-0.58). CONCLUSION: MAI is the strongest predictor of adjuvant systemic chemotherapy success. In patients with MAI < 3 (31% of all patients), ASCT does not improve survival.

Adult↗
PubMed2005

Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years.

PURPOSE: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) -negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. PATIENTS AND METHODS: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. RESULTS: Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (< 10, > or = 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P < or = .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P < .0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus > or = 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAI as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. CONCLUSION: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.

Adult↗
PubMed2005

Multivariate prognostic evaluation of the mitotic activity index and fibrotic focus in node-negative invasive breast cancers.

We validated with univariate and multivariate (Cox) analysis, the prognostic value of the mitotic activity index (MAI), the fibrotic focus (FF) and other prognosticators in 448 patients with lymph node-negative (LN-) invasive breast cancer <55 years without adjuvant systemic treatment (72.5 months median follow-up, range 4-119). Of these patients, 24.8% developed distant and 1.6% loco-regional recurrence. FF showed excellent inter-observer reproducibility (kappa = 0.93). Strong prognosticators were MAI, grade, nuclear atypia, FF and the St. Gallen criterion (SG). The subgroup with excellent survival selected by SG was only 16% of all patients, implying over-treatment of more than 70% of all LN- patients when using SG as adjuvant therapy selection criterion. If MAI <10, 13% showed distant metastases, contrasting with 41% if MAI > or = 10. FF was prognostic in the ductal and mixed ductal cancers, but not in the lobular and other subtype cancers. Patients with invasive (mixed) ductal cancers with FF absent, FF < 1/3 or FF > 1/3 of the tumour area, had distant metastasis rates of 17%, 35% and 48%; in MAI < 10 and FF absent, FF < 1/3 or FF > 1/3, metastasis rates were 11%, 13% and 42% and if MAI > or = 10, metastasis rates were 31%, 48% and 50%, respectively. In the 12 patients with MAI < 10 and a large FF > 1/3, event-free survival was similar to patients with MAI > or = 10. With multiple regression MAI < 10 versus > or = 10 is the strongest prognosticator (also stronger than the SG). The FF may be important as it has additional prognostic value to the MAI in the small subgroup of invasive ductal or mixed-ductal breast cancer patients with combined MAI < 10 and an FF > 1/3 of the tumour area.

Adult↗
PubMed2005

Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis.

Endometrial intraepithelial neoplasia (also known as 'EIN') is a precursor to endometrioid endometrial adenocarcinoma characterized by monoclonal growth of mutated cells, a distinctive histopathologic appearance, and 45-fold elevated cancer risk. We have applied diagnostic criteria for EIN to 97 successive endometrial biopsies classified as hyperplastic according to World Health Organization criteria and correlated results with computer-assisted morphometry (D-score) and clinical cancer outcomes. Three pathologists separately reviewed all cases for presence or absence of EIN using published criteria (gland area>stromal area, cytologic change in focus of altered architecture, lesion size>1 mm, and exclusion of cancer and mimics). Discordant cases were resolved by a consensus review at a multiheaded scope. Clinical outcomes were obtained in 84 patients from patient visit and pathology records. Diagnoses of presence or absence of EIN were unanimous among all three pathologists in 75% of cases, and intraobserver-reproducibility was very good (kappa 0.73-0.90). Cases rediagnosed as EIN encompassed hyperplasias previously diagnosed as atypical (n=18) or nonatypical (eight complex, two simple). Eight follow-up cancers were scattered between hyperplasia types (5/21 atypical, 3/63 nonatypical), but all classified as EIN (8/25) and D-score <or=1 (8/38). Subjective application of criteria for diagnosis of EIN correlates well with objective morphometry and successfully segregates patients into high and low cancer risk subgroups with better reproducibility than atypical hyperplasia diagnosis.

Diagnosis, Computer-Assisted↗
PubMed2005

Predictive testing of early CIN behaviour by molecular biomarkers.

Each year, 330,000 new Cervical Intraepithelial Neoplasias(CIN) occur in the European Union (EU) of which 120,000 are early CIN where grade (1, 2) indicates the progression-risk to CIN-3 and therefore determines the treatment choice. However, the Positive Predictive Value (PPV) of CIN grade to predict progression is low (10% and 20% for CIN-1 and -2 respectively, 16% on average) resulting in an enormous number of over-treatments indicating worrisome grade reproducibility.Certain molecular biomarkers such as Ki-67 have a higher PPV (30%, an improvement of 14%), which in Europe alone could improve treatment for many thousands of women per year with considerable cost reduction for the health care system. The quantitative Ki-67 prognostic model has been validated in independent retrospective and prospective studies from different laboratories. Moreover, the PPV of Ki-67 alone can be improved by additional molecular biomarkers (retinoblastoma protein = Rb, cytokeratins= CK-14/-13). Combined Ki67-Rb allows a 2-tiered progression-risk subgroup assignment as very low ( approximately 0% progression, 71% of all CIN-I/II patients)and high risk (48% progression risk, incidence 32%), leaving a small (7% of all) prognostically undetermined group (17% progression). Additional CK-14 and -13 analysis can sub-classify the high-risk in an intermediate and very high risk subgroup(with 40% and 100% progression risks respectively).Thus, molecular biomarkers are potentially important determinators of early CIN lesion behaviour. Important factors for widespread acceptance of molecular biomarkers are (1) market penetration by user-friendly equipment, (2) (inter)national keeping of GLP conditions (reproducibility, independent validation), requiring customer-driven industrial efforts,governmental measures, and additional PPV improvement to further reduce over-treatment.

Biomarkers, Tumor↗
PubMed2005

Use of biomarkers in the evaluation of CIN grade and progression of early CIN.

The treatment of cervical intraepithelial neoplasia (CIN) depends on the evaluation of CIN grade. The grading of CIN is however problematic, as intra- and interobserver reproducibility of CIN-grade evaluation among pathologists is not perfect. There are also difficulties in reliably distinguishing CIN from nonneoplastic lesions, and over- or undertreatment can be the result. These points suggest a need for adjuvant methods that can distinguish CIN from nonneoplastic lesions, and can distinguish different CIN grades and predict the risk of progression of early CIN1 and -2 lesions. This chapter describes the use of biomarker-related methods for the diagnosis and prognostic evaluation of patients with CIN1 and CIN2. As CIN involves the progressive dysfunction of proliferation and differentiation activities in cervical epithelial cells, we have concentrated in this chapter on demonstrating the utility of proliferation- and differentiation-related biomarkers.

Antibodies, Monoclonal↗
PubMed2005

Combined p53 and retinoblastoma protein detection identifies persistent and regressive cervical high-grade squamous intraepithelial lesions.

Most cervical high-grade squamous intraepithelial lesions (HSILs) persist, but approximately one third regress (ie, no HSIL in follow-up biopsies). To identify factors related to histologic proven persistence or regression. Twenty-eight small histologic (marker) biopsies with adequate follow-up were analyzed for human papillomavirus (HPV) genotypes and different immunoquantitative proliferation, cell cycle regulation, and differentiation markers. All cases had a biopsy-interval between the marker and first follow-up biopsy of at least 100 days (median, 8.2 months; range, 3.4-22.5 months). Follow-up was classified as regression or persistence. All lesions were high-risk (hr) HPV and p16 positive, 63% for HPV-16 or HPV-16 mixed with other hr genotypes, while 37% had other hrHPV types. The marker biopsies of the persistent HSILs had lower p53 and retinoblastoma protein (pRb) detected in the deep half of the epithelium (P = 0.001 and 0.02, respectively) than nonpersistent HSILs. The degree of positivity of p16, Ki-67, cyclin D1, lesion extent, positivity of the resection margins, and patient age were all unrelated to persistence or regression. Lesions with HPV-16 or mixed-16 genotypes had a significantly lower percentage of pRb (P = 0.02), p53 (P = 0.02), and cyclin D (P = 0.04) positive nuclei in the deep epithelial layers. In agreement with this, type-16 positive HSILs had a lower regression percentage than those with other HPV types, but the difference was not significant. HSILs with combined negativity/low positivity for p53 and pRb protein in small histologic biopsies are highly likely to persist, contrasting those in which one of these cell cycle regulators is strongly positive (p53 > 15%; pRb > 40%).

Adult↗
PubMed2004

Quantitative assessment of gastric antrum atrophy shows restitution to normal histology after Helicobacter pylori eradication.

BACKGROUND/AIMS: Grading gastric mucosal atrophy in antrum biopsy specimens remains a controversial subject because of limitations in interobserver agreement. We previously described a reliable, quantitative method for grading atrophy of the corpus mucosa with excellent reproducibility and good correlation with the Sydney scores. The aims of the present study were to evaluate the applicability of this method for the grading of antral atrophy and to study the effect of Helicobacter pylori eradication on the antral mucosa. METHODS: Antrum biopsy specimens were collected from 71 gastroesophageal reflux disease patients at baseline and after 3 and 12 months. After the first endoscopy, all subjects were treated with omeprazole 40 mg daily for 12 months. After randomization, 27 of the 48 H. pylori-positive patients additionally received eradication therapy. In 182 hematoxylin-eosin-stained specimens, which were of sufficient quality, the proportions (volume percentages) of glands (VPGL), stroma (VPS), infiltrate (VPI), and intestinal metaplasia in the glandular zone of the antrum mucosa were measured using a point-counting method. In these specimens, mucosal atrophy was assessed by two experienced gastrointestinal tract pathologists (E.B. and J.L.) according to the updated Sydney classification as either nonatrophic mucosa (n = 47) or as mild (n = 29), moderate (n = 50), or marked (n = 56) atrophy. In addition, a group of 23 cases with difficult-to-classify grades of atrophy were included. RESULTS: The mean VPGL decreased with increasing Sydney grades of atrophy (p < 0.001), while the mean VPS and VPI increased (both p < 0.001). After H. pylori eradication, even the cases with the lowest VPGL regressed to normal levels. CONCLUSIONS: Overall, a low VPGL correlates with increasing grades of antrum mucosal atrophy. The present data indicate that gastric mucosal atrophy is reversible, since almost all cases showed regression of VPGL after H. pylori eradication. The cases with difficult-to-classify grades of atrophy showed significantly lower VPGLs and higher VPIs than the reference cases.

Anti-Bacterial Agents↗
PubMed2004

Quantitative molecular parameters to identify low-risk and high-risk early CIN lesions: role of markers of proliferative activity and differentiation and Rb availability.

In early cervical intraepithelial neoplasia (CIN), the Ki67 stratification index 90th percentile (Si90) is a strong predictor of progression. This study was designed to further investigate the mechanisms leading to elevated Ki67 levels in lesions that progress and to try to improve the prognostic accuracy of Ki67-Si90. We studied 90 CIN lesions in which consensus existed regarding the grade between two experienced gynecologic pathologists. All CINs were p16-positive and showed Ki67 cell clusters above the lower third of the epithelium (both features diagnostic for CIN). Ki67 parameters, cell cycle regulators (Rb, p53, Cyclin A, E and D, p16, p21, p27, and telomerase), and cellular differentiation products (involucrin, CK13, CK14) were compared in the basal zone as well as the deeper and upper halves of the epithelium. Fifteen CIN cases (17%) progressed to a higher CIN grade, including 2 of 25 CIN1 (8%) and 13 of 65 CIN2 (20%) (these proportions of progressing CINs are similar to those in a large meta-analysis). Ki67 quantitation effectively predicted CIN progression as 0 of 40 "Ki67 low-risk" and 15 of 50 (30%) "Ki67 high-risk" lesions progressed. CIN progressors showed decreased Rb, CK13, CK14, and involucrin, but increased p21 and p27 expression. Ki67-Si90 and Rb in the deeper half of the epithelium (RbDeep) were the strongest multivariate independent predictors of progression. Ki67-Si90>0.57 was unfavorable, but only if it coexisted with RbDeep <45% (progression risk = 47%). All early CINs with combined Si90>0.57+RbDeep>45% or any Ki67-Si90 value below 0.57 were nonprogressors. In the high-risk progression subgroup (Ki67-Si90>0.57+RbDeep<45%), all cases with combined CK14<50% and CK13<80% (both in the basal cell layer) (4% of all lesions) progressed. We hypothesize that onco-HPV E7 expression reduces Rb, causing increased and upward proliferation (Ki67-Si90>0.57). Increased RbDeep can reduce proliferation, including its upward spread. Combined quantitation of Ki67, Rb, CK13, and CK14 gives accurate information about the progression risk of early CIN lesions.

Adult↗
PubMed2004

Ki67 predicts progression in early CIN: validation of a multivariate progression-risk model.

This study of early CIN biopsies (25 CIN1 and 65 CIN2) with long follow-up was done to validate, in a new group of patients, the value of Ki67 immuno-quantitative features to predict high CIN grade in a follow-up biopsy (often denoted to as "progression"), as described in a previous study. Each biopsy in the present study was classified with the previously described Ki67-model (consisting of the stratification index and the % positive nuclei in the middle third layer of the epithelium) as "low-risk" or "high-risk", and matched with the follow-up outcome (progression-or-not). Furthermore, it was studied whether subjective evaluation of the Ki67 sections by experienced pathologists, who were aware of the prognostic quantitative Ki67 features, could also predict the outcome. Thirdly, the reproducibility of routine use of the quantitative Ki67-model was assessed. Fifteen cases progressed (17%) to CIN3, 2/25 CIN1 (8%) and 13/65 CIN2 (20%), indicating that CIN grade (as CIN1 or CIN2) is prognostic and that the percentage of CIN1 and CIN2 cases with progression in the present study is comparable to many previous studies. However, the quantitative Ki67 model had stronger prognostic value than CIN grade as none of the 40 "Ki67-model low-risk" patients progressed, in contrast to 15 (30%) of the 50 "Ki67-model high-risk" patients (p<0.001). In multivariate analysis, neither CIN grade nor any of the other quantitative Ki67 features added to the abovementioned prognostic Ki67-model. Subjective analysis of the Ki67 features was also prognostic, although quantitative assessments gave better results. Routine application of the quantitative Ki67-model in CIN1 and CIN2 was well reproducible. In conclusion, the results confirm that quantitative Ki67 features have strong prognostic value for progression in early CIN lesions.

Adult↗
PubMed2004

The relationship between syntactic structure analysis features, histological grade and high-risk HPV DNA in cervical intraepithelial neoplasia.

AIM: To assess the correlation between syntactic structure analysis (SSA) features, revised dysplasia grade and the presence of high-risk human papillomavirus DNA in cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: HPV polymerase chain reaction (PCR) was assessed in 101 consecutive biopsies and consensus in CIN grade between the experts occurred in 88 cases (CIN1=16, CIN2=27, CIN3=45). SSA was performed in the diagnostic histological section of the CIN lesions in these patients and SSA features were compared with the blind review CIN grade, and presence/absence of high-risk HPV DNA. RESULTS: One of the SSA features (points from which the surrounding surfaces has 4 edges, PECO-4) was significantly different between all three consensus CIN grades. Many more features revealed significant differences between CIN1 and CIN2 or between CIN2 and CIN3 cases. With stepwise discriminant analysis, the best multivariate combination of features to distinguish the different CIN grades were the Maximum MST Line Length (MML) and the Area Disorder. Crude overall classification of the consensus grades with these features was 69%. The MML and the Area Disorder is also the best combination to distinguish cases with and without high-risk HPV DNA (77% correct classifications). CONCLUSIONS: SSA features are correlated with both CIN grade and presence of high-risk HPV DNA, but the discrimination power is not good enough to be used as a routine method for quality control of subjective grade or as a surrogate marker for high-risk HPV DNA presence.

Cell Transformation, Neoplastic↗
PubMed2003

Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1alpha (HIF-1alpha).

B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (> or =10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (<1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D1 (r=0.197, P=0.016). Further, in chi2 analyses, BCL-6-positivity was associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor-1alpha (P<0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed gains at the BCL-6 locus (3q27) in 14/86 (16%) breast cancer tissues. The cases with amplification in BCL-6 showed an increased (25%) incidence of BCL-6 protein overexpression. Thus, this study is the first to show that BCL-6 oncogene activation plays a role in cancers other than lymphomas.

Breast Neoplasms↗
PubMed2003

Prospective multicenter validation confirms the prognostic superiority of the endometrial carcinoma prognostic index in international Federation of gynecology and obstetrics stage 1 and 2 endometrial carcinoma.

PURPOSE: To validate the prognostic value of the endometrial carcinoma prognostic index (ECPI; combined myometrium invasion, flow cytometric DNA ploidy, and morphometric mean shortest nuclear axis [MSNA]) versus classic prognosticators. PATIENTS AND METHODS: Prospective multicenter ECPI analysis was conducted in 463 endometrial carcinomas with a median of 6.5 years (range, 1 to 10 years) follow-up, review of pathology features, and univariate (Kaplan-Meier) and multivariate (Cox) analyses. RESULTS: Initial routine and review diagnoses varied considerably (invasion depth, 11%; type, 20%; grade, 34%; vessel invasion, 72%); the review diagnoses were stronger prognostically. In International Federation of Gynecology and Obstetrics stage 1 (after histopathologic examination; pFIGO-1; n = 372; 38 deaths occurred as a result of disease [10.2%]), DNA ploidy was prognostic in hysterectomies (P <.00001) but not in curettages (P =.06). ECPI was a stronger prognostic indicator than other features. ECPI, MSNA, and DNA ploidy were also prognostic in pFIGO-1B and -1C subgroups. Multivariate analysis in pFIGO-1 showed that uterine MSNA < or = versus > 7.93 microm (hazard ratio [HR], 3.4) and grade (as 1 + 2 v 3; HR, 2.6) added to the ECPI (HR, 32), but only in patients with an unfavorable ECPI of > 0.87. Adjuvant radiotherapy was not an independent prognostic factor in any of the subgroups. In pFIGO-2 (n = 46), ECPI, DNA-ploidy, and age (< or = 64, > 64 years) were significant. In FIGO-3 (n = 31) and FIGO-4 (n = 14), none of the classic or other features analyzed was of prognostic value, which explains why in previous studies using different mixtures of FIGO stages, DNA ploidy prognostic results varied. CONCLUSION: In endometrial carcinoma, DNA-ploidy is prognostic in hysterectomy and not in curettage samples. The ECPI is prognostically much stronger than the classic features widely used for therapy triage in pFIGO-1 and -2.

Adult↗
PubMed2003

Barrett's adenocarcinomas resemble adenocarcinomas of the gastric cardia in terms of chromosomal copy number changes, but relate to squamous cell carcinomas of the distal oesophagus with respect to the presence of high-level amplifications.

Three different cancers predominantly occur at the gastro-oesophageal junction: squamous cell carcinomas of the distal oesophagus, adenocarcinomas of the distal oesophagus (Barrett's carcinomas), and adenocarcinomas of the gastric cardia. The aim of the present study was to investigate how, and to what extent, Barrett's carcinoma differs from adenocarcinoma of the gastric cardia on the one hand and squamous cell carcinoma of the distal oesophagus on the other, with respect to chromosomal aberrations and related gene expression. The present study analysed 14 squamous cell carcinomas, 24 Barrett's carcinomas, and 16 carcinomas of the gastric cardia. Comparative genomic hybridization revealed chromosomal abnormalities in all cases. Typical chromosomal aberrations for the squamous cell carcinoma type were gains at 3q and 11q13, and losses at 3p, 4q, 9p, 11q, and 13q. In contrast, typical copy number changes for both cardiac and Barrett's adenocarcinomas were gains at 2q, 7p, and 13q, and losses at 17p. High-level amplification occurred in all three groups, but its frequency in the cardiac carcinomas was lower than in the other two groups. In conclusion, squamous cell carcinomas are characterized by chromosomal aberrations which are distinct from those seen in carcinomas of the gastric cardia and in Barrett's adenocarcinomas. With respect to Barrett's cancer, the chromosomal aberrations more closely reflect the adenocarcinoma phenotype than the squamous origin of the epithelium.

Adenocarcinoma↗
PubMed2003

Low- and high-risk CIN 1 and 2 lesions: prospective predictive value of grade, HPV, and Ki-67 immuno-quantitative variables.

The aim of this study was to evaluate in small cervical biopsies (non-cone, non-large loop excision of the transformation zone, LLETZ) the prognostic value of both routinely assessed and reviewed cervical intraepithelial neoplasia (CIN) grades 1 and 2, oncogenic human papillomavirus (onco-HPV) DNA (HPV status) and Ki-67 immuno-quantitative features for the prediction of progression. In biopsies from 44 CIN patients (the learning set), subjective CIN grade, onco-HPV by PCR, and Ki-67 immuno-quantitative features were assessed. We followed development of the lesions by colposcopy and cytology, but the final endpoint was the histological grade (again in small biopsies). The outcome was defined as progression (histological (CIN 1 to (CIN 2 or 3)) or CIN 2 to CIN 3) or not (all other cases). Single and multivariate (Cox regression) and survival analyses were applied. The resulting predictive combination of quantitative features was then applied to a new test set of 35 consecutive CIN 2 (small) biopsies followed by large (cone or LLETZ) biopsies. In the learning set, mean follow-up of non-progression cases was 18.8 months (range 4.7-35.9), and of progression cases 13.1 months (range 6.4-32.9) (p = 0.18). Five cases progressed (11%). Of the 16 CIN 1 and 28 CIN 2 lesions, 31 cases (70%) were onco-HPV positive (5 of the CIN 1 and 26 of the CIN 2). The age of women with progression or not did not differ (p = 0.68). All 5 progression cases were CIN 2 (on review, one of these was reclassified as CIN 1), and positive for onco-HPV. Cox regression analysis showed that the percentage of Ki-67-positive cells located in the middle third layer of the epithelium (MIDTHIRD) and the 90th percentile of the stratification index (SI90) was the best combination to predict progression (log rank = 5.1, p = 0.02). Furthermore, sensitivity (100%), specificity (56%), positive predictive value (23%), negative predictive value (100%), and overall percentage correctly classified cases (61%) of this Ki-67 combination were higher than that of subjective CIN grade or HPV status, either single or combined (both for routine and review CIN grades). Adding CIN grade or HPV status did not improve the Ki-67 prognostic results. Application of the prognostic Ki-67 combination to the test set of 35 small biopsies followed by large (cone or LLETZ biopsies) gave comparable results. Analyses on homogeneous subgroups (CIN 2 only, onco-HPV+ only, or CIN2/onco-HPV+ only) gave similar results. In conclusion, Ki-67 immuno-quantitation of small biopsies showing CIN 1 or CIN 2 has strong independent prognostic value for progression.

Adult↗