Marie-Françoise Pelte

Important increase of invasive lobular breast cancer incidence in Geneva, Switzerland

A recent paper from the United States reported a sharp and unexplained increase in invasive lobular breast cancer incidence since 1977 (Li et al., Cancer 2000;88:2561–9). We investigated if this trend was also present in Geneva, Switzerland, where breast cancer incidence is one of the highest in Europe. We analyzed trends in breast cancer incidence according to histologic subtype, age and stage, to clarify the pattern. Our population‐based study includes all histologically confirmed invasive breast carcinomas (n = 6,247) recorded between 1976 and 1999 at the Geneva Cancer Registry. Breast histology was classified as ductal carcinoma, lobular carcinoma and other. Incidence trends were studied by log‐linear regression analyses. Models including effects of age, period and birth cohorts were used to describe rising incidence trends. The incidence of ductal carcinoma increased 1.2% per year (ptrend < 0.001) from 85.2 to 110.1/100,000. This increase concerned women aged 50–69 years and early‐stage tumors. Lobular cancer incidence increased disproportionately (14.4% per year, ptrend < 0.01) and rose from 2.9 to 20.5/100,000. This increase affected all age categories and both localized and advanced stages. In addition, a strong age‐cohort effect was present (p < 0.05), and women aged 50–59 years born after 1944 experienced the most marked increase. Our study shows a disproportionate increase of lobular breast cancer incidence compared to ductal cancer incidence. Contrary to ductal cancer, trends for lobular cancer are unlikely to be explained by increased use of screening mammography. Other explanations must be researched, in particular the role played by hormone replacement therapy.

Paget disease of the breast: findings at magnetic resonance imaging and histopathologic correlation.

Objectives:The purpose of this article is to describe magnetic resonance imaging (MRI) findings in patients with Paget disease of the breast and to evaluate mammography and MRI of the breast in the diagnosis of associated breast cancer. Materials and Methods:Nine patients with biopsy-proven Paget disease of the nipple underwent preoperative mammography and MRI of the breast to evaluate underlying breast cancer. All patients underwent subsequent surgery. The patients’ charts and imaging studies were retrospectively reviewed. Imaging findings were correlated to results of histopathology. Results:Histopathology confirmed Paget disease of the nipple in all 9 patients and diagnosed associated ductal carcinoma in situ (DCIS) in the retroareolar lactiferous ducts in 8 of 9 patients (88%). MRI showed abnormal nipple enhancement in these 8 patients with an ill-defined thickened nipple–areolar complex. DCIS elsewhere in the breast was diagnosed in 4 of 9 patients (45%) corresponding to nonfocal enhancement in all 4 patients at MRI of the breast (100%). Conclusions:Paget disease of the breast associated with underlying DCIS can be diagnosed at MRI of the breast and therefore impact management decisions.

Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis

Mutations in tumor‐suppressor gene BARD1 have been found in inherited and spontaneous breast, ovarian and uterine cancers. BARD1 plays a critical role in DNA repair and ubiquitination as binding partner of BRCA1, with which it colocalizes to nuclear dots. Independently of BRCA1, BARD1 can induce p53‐dependent apoptosis in response to genotoxic stress. Therefore, BARD1 or p53 might be defective in cancer cells spared from apoptosis. We investigated BARD1 and p53 expression in ovarian, breast and non‐small‐cell lung cancers. BARD1 expression was highly upregulated and cytoplasmic in most cancer cells, while weak nuclear staining was observed in the surrounding normal tissue. Maximal BARD1 expression was associated with the most malignant ovarian cancer, clear cell carcinoma. In breast cancer, BARD1 expression was correlated with poor differentiation and large tumor size, established factors of poor prognosis, as well as short disease‐free survival. In contrast to breast and ovarian cancers, no correlation of BARD1 expression with either grade or stage could be determined for lung cancer. RT‐PCR, performed on 10 ovarian cancers, revealed absence of the 5′ portion of the BARD1 transcript in 7 tumors, and sequencing of the remaining 3 identified a missense mutation (A1291G) resulting in an amino acid change of glutamine 406 to arginine. These data suggest that genetic and epigenetic changes might lead to elevated cytoplasmic expression of BARD1 and that cytoplasmic BARD1 might be a poor prognostic factor for breast and ovarian cancers.

Young patients with endometrial cancer: How many could be eligible for fertility-sparing treatment?

OBJECTIVES To assess the characteristics of young women with endometrial carcinoma, and evaluate those potentially eligible for conservative therapy. METHODS We identified women diagnosed with endometrial cancer between 1970 and 2005 at the population-based Geneva Cancer Registry (n=1365). We classified patients into two age groups (< or =45 and >45 years old). Differences in demographic, tumor, diagnostic and treatment characteristics were tested with chi square. Kaplan-Meier analysis was used to calculate survival from endometrial cancer and the log-rank test to analyze differences in survival between the two groups. RESULTS The young group comprised 44 (3.2%) women and the old group 1321 (96.8%) women. Synchronous ovarian malignancies were found in six patients (14%) in the young group, compared with 23 (2%) in the old group (P<0.001). Tumor stage was also different between the two groups, principally because of more stage II among the young (P=0.012). Histological tumor type, grade and specific endometrial cancer 5-year survival did not significantly differ between the two groups. According to final histopathologic evaluation, eight patients from the young group had FIGO stage IA, grade I disease, i.e. may have been eligible for fertility-sparing treatment, corresponding to an incidence rate of 0.3/100,000. CONCLUSION No significant difference regarding tumor characteristics and survival between young and older patients was observed, except stage of disease and rate of synchronous ovarian malignancy. Conservative approach is a meaningful quality of life goal for patients with cancer, but only suitable for a limited number of patients.

Value of immunohistochemistry in staging T1 urothelial bladder carcinoma

PURPOSE The subclassification of T1 bladder tumors into T1A and T1B has an important prognostic significance and a great impact on patient management. Unfortunately, staging T1 tumors is highly subject to interpathologist variation that can be critical for patients included in randomized clinical trials. To determine the value of immunohistochemistry (IHC), such as desmin and keratin, in comparison to hematoxylin-eosin (H&E) in classifying T1 stage disease, we retrospectively examined 93 consecutive cases diagnosed at our department. MATERIALS AND METHODS The study was conducted in two phases (H&E then IHC), each in two time periods. First H&E, and then IHC slides were reviewed independently by two experienced pathologists and discrepant cases from each phase were discussed between the two pathologists to reach a final decision. RESULTS The two methodologies (H&E and IHC) showed total agreement in 76 out of 93 cases. IHC downstaged seven cases, that is from T1B to T1A, upstaged four cases, that is from T1A to T1B, lowered the rate of imprecision and eliminated the disagreement between the two pathologists. However, IHC failed to subclassify T1 tumors in three cases. Finally, the discussion supported by the IHC was very useful in reaching the diagnosis in some cases. CONCLUSIONS IHC appears to be a useful tool in staging T1 bladder cancer, especially in difficult cases where specimen orientation and artifact could create a major hindrance in reaching an accurate diagnosis.

Importance and determinants of Gleason score undergrading on biopsy sample of prostate cancer in a population-based study

BackgroundIn this population-based study, we investigated the degree of concordance between Gleason scores obtained from prostate biopsies and those obtained from prostatectomy specimens, as well as the determinants of biopsy understaging.MethodsWe considered for this study all 371 prostate cancer patients recorded at the Geneva Cancer Registry diagnosed from 2004 to 2006 who underwent a radical prostatectomy. We used the kappa statistic to evaluate the Gleason score concordance from biopsy and prostatectomy specimens. Logistic regression was used to determine the parameters that predict the undergrading of the Gleason score in prostate biopsies.ResultsThe kappa statistic between biopsy and prostatectomy Gleason score was 0.42 (p < 0.0001), with 67% of patients exactly matched, and 26% (n = 95) patients with Gleason score underestimated by the biopsy. In a multi-adjusted model, increasing age, advanced clinical stage, having less than ten biopsy cores, and longer delay between the two procedures, were all independently associated with biopsy undergrading. In particular, the proportion of exact match increased to 72% when the patients had ten or more needle biopsy cores. The main limitation of the study is that both biopsy and prostatectomy specimens were examined by different laboratories.ConclusionsThe data show that concordance between biopsy and prostatectomy Gleason scores lies within the classic clinical standards in this population-based study. The number of biopsy cores appears to strongly impact on the concordance between biopsy and radical prostatectomy Gleason score.

Magnetic resonance imaging to identify risk of lymph node metastasis in patients with endometrial cancer

To assess the value of magnetic resonance imaging (MRI) to identify endometrial cancer patients at risk of lymph node metastasis.

Diverse glandular pathologies coexist with high-grade squamous intraepithelial lesion in cyto-histological review of atypical glandular cells on ThinPrep specimens

Objective:  To identify in cytology, high‐grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high‐grade cervical intraepithelial lesion in histology.

Primary breast lymphomas

The diagnosis, prognostic factors, and optimal management of primary breast lymphomas (PBL) is difficult. Seven patients recorded at the Geneva Cancer Registry between 1973–1998 were reviewed. Five patient had diffuse large B-cell lymphoma, one a follicular lymphoma and one a MALT-lymphoma. All patients had clinical and radiological findings consistent with breast cancer and underwent mastectomy, which is not indicated in PBL. Diagnosis should be established prior to operative interventions, as fine needle aspiration missed the diagnosis for one patient and intra-operative frozen sections for 3 patients in our study. Five-year and 10-year overall survivals were 57% and 15%, respectively. Of the 3 patients who died from PBL, 2 had tumors that were Bcl-2 positive but Bcl-6 negative. All 3 surviving patients have positive Bcl-2 and Bcl-6 immunostaining, which could be important prognostic factors if confirmed by a larger study.

Increased risk of second cancer among patients with ovarian borderline tumors

OBJECTIVES Several studies have demonstrated a higher risk of colorectal and breast cancers subsequent to invasive ovarian cancer. Such risk has not been investigated for ovarian borderline tumors. We aim to evaluate the risk of subsequent cancer occurrence among patients with borderline ovarian tumors in a population-based setting. METHODS We identified 171 patients with a diagnosis of borderline ovarian tumors recorded at the Geneva Cancer Registry, Switzerland. We calculated age and period standardized incidence ratios (SIR) of second tumor occurrence by dividing the number of observed cases by the number of expected cases in the cohort, using cancer incidence rates of the general female population. RESULTS The risk of developing second cancer was 1.85-fold (95% Confidence Interval [CI]: 1.10-2.92, n=16) higher among women with borderline ovarian tumors compared to that expected in the general population. The excess of risk primarily concerned colorectal cancer (SIR: 3.97, CI: 1.38-12.95, n=5) and breast cancer (SIR: 2.09, CI: 0.84-4.31, n=7), but the latter result was not statistically significant (p=0.09). The increased risk of developing second cancer was mainly observed among patients diagnosed with ovarian borderline tumors occurring before the age of 50. These results were not explained by surveillance bias or by metastasis from one site to another. CONCLUSION Women with ovarian borderline tumors have an increased risk of developing secondary cancer, particularly colorectal cancer. These results point to potential common risk factors for these tumors and ask for close surveillance of patients with borderline ovarian tumors.