ABSTRACT
OBJECTIVE: To calculate the cumulative risks and incidence rates for the development of multiple (two or more) basal cell carcinomas (BCC). DESIGN: A retrospective cohort study with data from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. METHOD: Using pathology reports, the first 2483 patients diagnosed with a first histologically confirmed BCC in the year 2004 were retrospectively followed for 5 years. The Andersen-Gill survival analysis was used to study whether gender or age affected the risk of developing multiple BCCs. RESULTS: In total, 2483 patients developed 3793 BCCs. The five-year cumulative risk of developing multiple BCCs was 29.2%. The incidence rate for the development of two or more BCCs was 25,318 per 100,000 person-years in the first half year after first BCC diagnosis, decreasing to 6953 per 100,000 person-years after 5 years of follow-up. Compared with women men had a 30% (adjusted HR 1.30; 95% CI 1.11-1.53) higher risk of developing multiple BCCs and those aged 65-79 years had an 80% (adjusted HR 1.81; 95% CI 1.37-2.41) higher risk of having two or more BCCs compared with patients younger than 50 years. CONCLUSION: Almost one third of the patients with a BCC developed two or more BCCs, most frequently in the period shortly after the first BCC. At diagnosis of BCC a full body skin examination should be performed and repeated annually for at least three years.
Subject(s)
Carcinoma, Basal Cell/diagnosis , Registries , Skin Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/epidemiology , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Retrospective Studies , Risk , Skin Neoplasms/epidemiology , Survival AnalysisABSTRACT
We examined the validity of immunohistochemistry for mismatch repair (MMR) proteins in colorectal cancer specimens to identify patients at risk for Lynch syndrome (hereditary nonpolyposis colorectal cancer) and patients with sporadic microsatellite instable colorectal cancer. This was assessed by observer agreement for and accuracy of interpretation of immunohistochemistry. Seven pathologists from 5 different pathology laboratories evaluated 100 molecularly defined colorectal cancers stained for MLH1, PMS2, MSH2, and MSH6. Two of the pathologists were experienced in interpretation of immunohistochemistry for MMR proteins. After evaluation of a subset of 20 cases, a discussion meeting was organized, after which pathologists evaluated all 100 cases. Staining patterns were interpreted as aberrant, normal, or indefinite. In 82% of tumors, 5 or more pathologists reached the same interpretation, which was considered the consensus diagnosis. Consensus was reached slightly less frequently in microsatellite instable than in stable tumors, and interobserver variation was moderate to substantial (kappa: 0.49-0.79). More microsatellite instable tumors showed an indefinite staining pattern compared with microsatellite stable tumors. Three out of 7 pathologists, including the 2 experienced pathologists, did not miss a microsatellite instable tumor. Each pathologist found at least 1 tumor with an aberrant staining pattern, whereas consensus was a normal staining pattern and the tumor was microsatellite stable. We conclude that, if restricted to experienced pathologists, immunohistochemistry is a valid tool to identify patients at risk for Lynch syndrome and patients with sporadic microsatellite instable colorectal cancer. An indefinite or aberrant staining result has to be followed by molecular microsatellite instability analysis to confirm the presence of a defective DNA MMR system.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/enzymology , Colorectal Neoplasms/enzymology , DNA Mismatch Repair , DNA Repair Enzymes/analysis , Immunohistochemistry , Adaptor Proteins, Signal Transducing/analysis , Adenosine Triphosphatases/analysis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , DNA-Binding Proteins/analysis , Gene Expression Regulation, Neoplastic , Germany , Humans , Microsatellite Instability , Mismatch Repair Endonuclease PMS2 , MutL Protein Homolog 1 , MutS Homolog 2 Protein/analysis , Netherlands , Nuclear Proteins/analysis , Observer Variation , Predictive Value of Tests , Reproducibility of ResultsABSTRACT
PURPOSE: This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. METHODS: Patients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome, hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital setting were explored with logistic regression modeling. RESULTS: Thirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic. CONCLUSION: The referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in nonteaching hospitals.
