Biomedical subjects

Axel Hoos

Publications and source records attributed to Axel Hoos.

22 records · Page 2Linked to original sources

PubMed2002

Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by chemotherapy and radiotherapy.

The presence of focal endocrine cells in colorectal adenocarcinoma is a relatively common phenomenon. However, endocrine differentiation in treated adenocarcinomas of the gastrointestinal tract has received little attention. We noted striking numbers of cells with endocrine morphology and phenotype in the residual tumor of six randomly encountered cases of rectal adenocarcinoma that were subjected to neoadjuvant therapy. All six cases had a substantial treatment response (> or =50%). To validate our initial observation and to explore its clinicopathologic significance, further morphologic and immunohistochemical studies were performed on 53 cases of rectal adenocarcinomas treated with preoperative radiation with (33 cases) or without (20 cases) chemotherapy. Pretreatment biopsies from 20 of the 53 cases and 79 resection specimens of rectal adenocarcinoma that received no neoadjuvant therapy were used as controls. Chromogranin positivity was identified in the posttreatment resection specimens in 36 of the 53 study cases (67.9%). Twenty of the 36 showed positive staining in > or =20% of the residual tumor cells. The chromogranin-positive cells in these cases often formed cords or nests. On hematoxylin and eosin sections these cells had markedly eosinophilic cytoplasm and round and uniform or sometimes pleomorphic nuclei with an often dense chromatin pattern. The proportion of chromogranin-positive cells was significantly associated with the extent of treatment response (p = 0.0005). Tumors treated with both chemotherapy and radiotherapy were more likely to have abundant chromogranin-positive cells compared with tumors treated with radiotherapy alone (p = 0.0004). In contrast, only 30% of the pretreatment biopsies and 17.7% of the control resection specimens of untreated rectal carcinomas showed chromogranin-positive cells, predominantly arranged as scattered individual positive cells, constituting <10% of the tumor. No significant correlation was observed between pretreatment and posttreatment specimens with regard to chromogranin positivity (p = 1.0). Ten of 15 patients (66.7%) whose resection specimens showed positive chromogranin staining failed to demonstrate any chromogranin positivity in their pretreatment biopsy specimens. In addition, groups or nests of chromogranin-positive cells noted in posttreatment specimens showed a very low Ki67 labeling index (<5%) but showed a frequency of abnormal p53 protein expression comparable with that observed in tumor foci resembling conventional adenocarcinoma (66.7% vs 62.5%). Our findings demonstrate that there is an increased frequency and density of cells with an endocrine phenotype in rectal adenocarcinomas that were subjected to neoadjuvant therapy and that the extent of endocrine cells appears proportional to the degree of treatment response. The possible mechanism for the increased endocrine cells in treated rectal adenocarcinomas may be related to induction of endocrine differentiation in tumor cells by cytotoxic insult.

Adenocarcinoma↗

PubMed2002

Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas.

OBJECTIVE: To define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. METHODS: The authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. CONCLUSIONS: Positive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.

Adolescent↗

PubMed2002

p63 expression profiles in human normal and tumor tissues.

PURPOSE: The p63 gene, located on chromosome 3q27-28, is a member of the p53 gene family. The product encoded by the p63 gene has been reported to be essential for normal development. EXPERIMENTAL DESIGN: In this study, we examined the expression pattern of p63 in human normal and tumor tissues by immunohistochemistry using a monoclonal antibody (clone 4A4) that recognizes all p63 splice variants, and by reverse transcription-PCR using isoform-specific primers. RESULTS: We found that p63 expression was restricted to the nucleus, with a nucleoplasmic pattern. We also observed that the expression was restricted to epithelial cells of stratified epithelia, such as skin, esophagus, exocervix, tonsil, and bladder, and to certain subpopulations of basal cells in glandular structures of prostate and breast, as well as in bronchi. Consistent with the phenotype observed in normal tissues, we found that p63 is expressed predominantly in basal cell and squamous cell carcinomas, as well as transitional cell carcinomas, but not in adenocarcinomas, including those of breast and prostate. Interestingly, thymomas expressed high levels of p63. Moreover, a subset of non-Hodgkin's lymphoma was also found to express p63. Using isoform-specific reverse transcription-PCR, we found that thymomas express all isoforms of p63, whereas the non-Hodgkin's lymphoma tended to express the transactivation-competent isoforms. We did not detect p63 expression in a variety of endocrine tumors, germ cell neoplasms, or melanomas. Additionally, soft tissue sarcomas were also found to have undetectable p63 levels. CONCLUSIONS: Our data support a role for p63 in squamous and transitional cell carcinomas, as well as certain lymphomas and thymomas.

Alternative Splicing↗

PubMed2002

Tissue microarray molecular profiling of early, node-negative adenocarcinoma of the rectum: a comprehensive analysis.

PURPOSE: Early-stage adenocarcinoma of the rectum treated with curative intent has a favorable overall prognosis; however, 20%-30% of the patients recur, and the majority ultimately die of disease. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors accounting for their more aggressive biological behavior. This study evaluates such molecular phenotypes with regard to cell cycle regulation and proliferation and determines their significance for patient outcome. EXPERIMENTAL DESIGN: One hundred patients with primary T(2-3), N(0) adenocarcinoma of the rectum uniformly treated by surgery alone were studied. Core biopsies of pathological specimens were assembled on tissue microarrays, and expression of p53, mdm-2, p21, Bcl-2, p27, cyclin D1, and Ki-67 was analyzed by immunohistochemistry. Molecular profiles were correlated with disease-free (DFS) and disease-specific survival (DSS). RESULTS: Despite previously described prognostic relevance of some of the investigated molecules in analyses where different stages of colorectal cancer were included, none of the cell cycle-regulatory or proliferation-related markers was associated with recurrence or survival. However, patients with tumors demonstrating down-regulation of p27, a cyclin-dependent kinase inhibitor and tumor suppressor gene associated with development of metastases, showed a trend toward reduced DFS and DSS (P = 0.06 and P = 0.07, respectively). CONCLUSIONS: In this homogeneous group of patients with early-stage, node-negative adenocarcinoma of the rectum uniformly treated by surgery alone, the investigated cell cycle-regulatory and proliferation-associated proteins appear to have no prognostic significance. However, down-regulation of p27 appears to be associated with a trend toward reduced DFS and DSS, which suggests further investigation of other p27-related pathways potentially relevant for metastatic disease.

Adenocarcinoma↗