Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.

Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression profiling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by expression profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

The Introduction of Adult Appendicitis Score Reduced Negative Appendectomy Rate.

BACKGROUND AND AIMS: Implementation of a clinical risk score into diagnostics of acute appendicitis may provide accurate diagnosis with selective use of imaging studies. The aim of this study was to prospectively validate recently described diagnostic scoring system, Adult Appendicitis Score, and evaluate its effects on negative appendectomy rate. MATERIAL AND METHODS: Adult Appendicitis Score stratifies patients into three groups: high, intermediate, and low risk of appendicitis. The score was implemented in diagnostics of adult patients suspected of acute appendicitis in two university hospitals. We analyzed the effects of Adult Appendicitis Score on diagnostic accuracy, imaging studies, and treatment. The study population was compared with a reference population of 829 patients suspected of acute appendicitis originally enrolled for the study of construction of the Adult Appendicitis Score. RESULTS: This study enrolled 908 patients of whom 432 (48%) had appendicitis. The score stratified 49% of all appendicitis patients into high-risk group with specificity of 93.3%. In the low-risk group, prevalence of appendicitis was 7%. The histologically confirmed negative appendectomy rate decreased from 18.2% to 8.7%, p<0.001, compared to the original dataset. CONCLUSION: Adult Appendicitis Score is a reliable tool for stratification of patients into selective imaging, which results in low negative appendectomy rate.

No MSH6 germline mutations in breast cancer families with colorectal and/or endometrial cancer.

BACKGROUND: The genetic background in breast cancer families with colorectal and/or endometrial cancer is mostly unknown. The functional connection between MSH6 and the known breast cancer predisposition gene product BRCA1 suggests that the MSH6 gene may also play a role in breast cancer predisposition. METHODS: We analysed 38 breast cancer families with colorectal and/or endometrial cancer for germline mutations in MSH6. RESULTS: No disease associated mutations were detected among the breast cancer families. However, mutation analysis revealed a Glu995STOP mutation in an atypical HNPCC family. The same mutation was found in a patient with both breast and colorectal carcinoma in our previous study, and haplotype analysis confirmed a common ancestral origin. The Glu995STOP mutation was further examined in an extensive series of 245 colorectal and 142 breast carcinoma patients with a family history of breast, colorectal, and/or endometrial carcinoma, and in 268 healthy population controls, but none was found to carry the mutation. CONCLUSIONS: Our results suggest that MSH6 may not be the underlying gene in breast cancer families with a history of colorectal and/or endometrial cancer. The Glu995STOP founder mutation is not a familial breast cancer predisposition allele and makes only a limited contribution to colorectal cancer burden in Finland.

Feasibility of axillary ultrasound in the quality assessment of sentinel node biopsy in breast cancer surgery.

BACKGROUND AND AIMS: The purpose of this study was to evaluate the efficacy of high-resolution axillary ultrasound (AU) in detecting the rate of recurrence after a negative sentinel node (SN) biopsy in patients with breast cancer and without additional axillary dissection. MATERIALS AND METHODS: The operating oncologic surgeon performed 196 consequent sentinel node biopsies during surgery of breast cancer. The sentinel nodes were identified by using preoperative lymphoscintigraphy, intraoperative gamma probe and Patent Blue dye. A routine postoperative follow-up of the patients were performed every 3rd month including clinical examinations, blood chemistry and mammography. After 31 months (range 14-49 months), a high-resolution AU was performed for 107 patients with a negative sentinel node during surgery and without axillary dissection, to visualize any abnormal lymph nodes in the axilla. If necessary, large core biopsies were undertaken to obtain histology of abnormal axillary nodes. RESULTS: The SNs were visualized during preoperative lymphoscintigraphy in 167/196 (85%) and found during the surgery in 163/167 (98%) of patients. The mean number of removed SN were 1.7+/-0.8. The SN metastasis were found in 29% (56/196) of patients. During the follow-up, abnormal nodes were identified during AU in only 4/107 patients. Core biopsies confirmed benign histology in three patients and one case of lymphoma was detected. CONCLUSIONS: There were no axillary recurrences of breast cancer after a negative SN biopsy during the 2.6 year follow-up. Axillary ultrasound is a useful tool in the quality control of patients with negative SN biopsy and without diagnostic axillary dissection.