Uterine serous carcinoma: a historic evaluation of therapy.

UNLABELLED: Summary OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive, histological subtype of endometrial cancer with a poor prognosis. This study evaluates the additional effect of staging surgery above total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH+BSO) on the use of adjuvant therapy and subsequent survival outcomes in clinical early-stage USC patients. MATERIALS AND METHODS: This retrospective cohort study includes 75 women treated for clinical early-stage USC. RESULTS: In 33 (44%) clinical early-stage patients surgical staging was performed and 15 patients (45%) proved to have lymphatic or abdominal metastasis. Use of adjuvant therapy was similar in patients, both staged with no metastasis (n = 18) and patients who underwent TAH and BSO only (n = 42, p = 0.17). No significant survival difference was found between surgically staged and TAH+BSO patients. CONCLUSIONS: Surgical staging proved to be important to determine stage of disease and hence prognosis. Surgical staging did not lead to selective avoidance of adjuvant therapy in patients with no metastasis.

Assessment of apoptosis by M30 immunoreactivity and the correlation with morphological criteria in normal colorectal mucosa, adenomas and carcinomas.

AIMS: To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in-situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase-cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard. METHODS AND RESULTS: Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 +/- 0.04% in normal mucosa, 0.42 +/- 0.04% in adenomas and 1.97 +/- 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 +/- 0.03%, 0.62 +/- 0.06% and 1.78 +/- 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P < 0.01). CONCLUSION: Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma-carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.

Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds.

The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an APC gene mutation and a mismatch repair gene (for example, MLH1) mutation has never been described. In the present case report, we report rapidly progressive adenomatous polyposis in a 10 year old boy with a germline frame shift mutation in the APC gene and a germline splice site mutation in the MLH1 gene. Immunohistochemical investigations showed abnormal expression of beta-catenin in early adenomas with low grade dysplasia, attributed to the APC gene mutation. Subsequent loss of function of the MLH1 gene, as shown by absent immunostaining of its protein in adenomas with high grade dysplasia, may well have caused the rapid progression to high grade dysplasia in many of the adenomas.

Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is thought to arise from adenomas. HNPCC mostly occurs in the proximal colon. We investigated whether this proximal preponderance is due to a proximal preponderance of adenomas or (also) differences in transformation rates from adenomas to cancer between the distal and proximal colon. METHODS: A total of 100 HNPCC adenomas were evaluated and compared with 152 sporadic adenomas for location, size, and dysplasia. Twenty five adenomas from patients with a known mismatch repair (MMR) gene mutation were stained for expression of MLH1 and MSH2. RESULTS: HNPCC adenomas were more often located proximally (50% v 26%; p=0.018) and were smaller in comparison with sporadic adenomas. They were similarly dysplastic. However, all proximal HNPCC adenomas > or =5 mm were highly dysplastic compared with 17% of the larger proximal sporadic polyps (p<0.001). They were also more often highly dysplastic than larger distal HNPCC adenomas (p<0.001). Small HNPCC adenomas were, except for their location, not different from sporadic adenomas. Fifteen of the 25 "known mutation" adenomas showed loss of expression of either MLH1 or MSH2. The 10 adenomas with expression were all small with low grade dysplasia. CONCLUSION: HNPCC adenomas are located mainly in the proximal colon. The progression to high grade dysplasia is more common in proximal than distal HNPCC adenomas, indicating a faster transformation rate from early adenoma to cancer in the proximal colon. MMR gene malfunction probably does not initiate adenoma development but is present at a very early stage of tumorigenesis and heralds the development of high grade dysplasia.