Biomedical subjects

R Holm

Publications and source records attributed to R Holm.

154 records · Page 9Linked to original sources

PubMedDate not supplied

Epidermal growth factor receptor expression has no independent prognostic significance in advanced ovarian cancer.

BACKGROUND: This study was undertaken to evaluate whether overexpression of epidermal growth factor receptor (EGFR) was of possible prognostic and/or predictive significance in advanced ovarian cancer. STUDY DESIGN: Tumor specimens from 185 patients with stage III ovarian cancer, treated at the Department of Gynecologic Oncology of the Norwegian Radium Hospital, were examined immunohistochemically for overexpression of EGFR. Response was verified with second look laparotomy in 149 patients after 4 courses of platinum/anthracyclin chemotherapy. Correlations between EGFR status and classical clinicopathological parameters were examined, and uni- and multivariate survival analysis was performed. RESULTS: EGFR membrane immunostaining was observed in 22% of the cases. EGFR overexpression correlated positively with residual disease after first surgery (P = 0.048) and tended to correlate with increasing FIGO substage (P = 0.058). No correlation was found with response to chemotherapy. In univariate analysis age below the median, FIGO substage, residual disease, histology, differentiation grade and the presence of ascites correlated with disease-related survival. A tendency towards correlation was found for EGFR (P = 0.0669). In muitivariate analysis only residual disease, histological type, differentiation grade and the presence of ascites retained independent prognostic significance. CONCLUSION: EGFR status was found to be of no independent prognostic or predictive significance in this large group of uniformly treated stage III ovarian cancer patients.

Adult↗

PubMedDate not supplied

P-glycoprotein expression is a marker for chemotherapy resistance and prognosis in advanced ovarian cancer.

BACKGROUND: It was our aim to study the prevalence and possible prognostic and predictive significance of the expression of P-glycoprotein, a transmembrane transport protein related to classical multidrug resistance, in patients with advanced ovarian cancer. STUDY DESIGN: Tumor tissue from 73 previously untreated patients with FIGO stage 3 ovarian cancer was examined with immunohistochemistry for the expression of P-glycoprotein before and after chemotherapy. Response to 4 cycles of combination chemotherapy with cisplatin and epirubicin was assessed with second look laparotomy. The log rank test was used for univariate survival and the Cox proportional hazards regression model for multivariate survival analysis. RESULTS: P-glycoprotein expression was detected in 47% of untreated cases, and correlated with unfavourable prognostic factors such as advanced age, presence of ascites and larger residual disease deposits after primary surgery. P-glycoprotein negative cases responded significantly better to chemotherapy (P < .001). In the multivariate survival analysis P-glycoprotein expression was an independent predictor of both overall (P = .045) and progression free (P = .006) survival. When P-glycoprotein expression and residual disease status were considered together, the patients could be divided in three clearly distinct prognostic groups (P = .0009). CONCLUSION: P-glycoprotein expression is a predictor of response and survival in a uniformly treated and followed cohort of advanced ovarian cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Squamous cell carcinomas, an immunohistochemical and ultrastructural study.

Fourty-seven squamous cell carcinomas (SCCs) were studied by light microscopy, immunohistochemistry and electronmicroscopy. Nineteen percent (9 cases) of SCCs in different locations were immunoreactive for CAM5.2 and three poorly differentiated SCCs did not express cytokeratins 6 and 18. No cases were positive for c-erbB2 protein. p53 protein overexpression was found in malignant cells in 40% of the primary tumours and in 60% of the lymph node metastases. Four poorly differentiated SCCs expressed vimentin and in these cases the tumour cells had accumulations of less dense intermediate filaments in cytoplasm.

Biomarkers, Tumor↗

PubMedDate not supplied

Deregulation of D-type cyclins in uterine cancers. Cyclin D1/D3 is differentially expressed in cervical cancer.

BACKGROUND: We have previously found cyclin D1 to be overexpressed in 45% of corpus cancers, but in only 3% of cervical cancers. To see whether and how D-type cyclins contribute to the neoplastic phenotype in uterine cancers, aberrant expression and association between cyclins D1 and D3 proteins were studied. MATERIALS AND METHODS: Expression of cyclin D3 was investigated by immunohistochemistry in 51 patients with primary cancer of the corpus and 73 cases of primary cervical carcinomas. Amplification of the cyclin D1 and D3 genes was investigated by fluorescence in situ hybridisation (FISH). RESULTS: We found high/moderate levels of cyclin D3 in 53.5% of cervical cancers and 55% of corpus cancers. High/moderate expression of cyclin D1 and D3 was associated in the corpus cancers, but not in cervical cancers. The accumulation of cyclin D3 but not D1 protein could, in some cases, be explained by increased gene dosage since extra copies of chromosome 6 were found. CONCLUSION: This study demonstrates that in cervical cancers cyclin D3 may compensate for low levels of cyclin D1, whereas in corpus cancers both isoforms may contribute to the neoplastic phenotype.

Cyclin D1↗

PubMedDate not supplied

C-erbB-2 protein and neuroendocrine expression in breast carcinomas.

90 primary breast carcinomas and 18 metastases were immunostained for c-erbB-2 protein and neuron specific enolase. 30 tumours were c-erbB-2 negative and NSE positive, 23 tumours were NSE negative and c-erbB-2 positive. 1 tumour expressed focal immunoreactivity for both markers. 54 of the 108 tumours (50%) did not express either marker. Hormone immunoreactivity was present in single cells and in small groups of cells in 18 of the 31 NSE positive tumours. Bombesin, neurotensin and prealbumin were present in 4 cases each, followed by beta-endorphin and VIP in 3 cases each, leu-enkephalin in 2 cases and gastrin, serotonin, substance P, glucagon and somatostatin in 1 case each. None of 10 NSE negative breast carcinomas were comprised of cells expressing immunoreactivity for hormones. By immunoelectron microscopic examination the c-erbB-2 protein was shown to be present on the cell membrane, on smooth areas, microvilli and in coated pits. Immunoreactivity was also expressed in vesicles in cytoplasm and along rough endoplasmic reticulum. The study shows that c-erbB-2 protein expression and neuroendocrine activity are present in different tumour cell populations. This supports the hypothesis that the presence of c-erbB-2 protein, indicating an elevated cellular tyrosine kinase activity with stimulation of growth, intracellular Ca++, and phosphatidylinositol derivates, means that the same cell does not need regulation of the same factors by stimulation of peptide hormone receptors. Thus the production of autocrine and paracrine factors is switched off.

Biomarkers, Tumor↗

PubMedDate not supplied

p53 protein expression in squamocellular carcinomas of the lip.

Twenty-six cases of squamocellular carcinomas of the lip were immunostained for p53 protein. Nuclear accumulation of p53 protein was observed in 88% of the 26 carcinomas, in 64% of adjacent "normal" epithelium and in all four cases with adjacent atypical squamous epithelium. 93% of the specimens (13/14) with p53 protein accumulation in "normal" epithelium demonstrated evidence of solar elastosis. UV radiation may induce p53 gene mutation as an early event in the neoplastic transformation.

Aged↗

PubMedDate not supplied

Undifferentiated carcinoma: an immunohistochemical and ultrastructural study.

Twenty-eight undifferentiated carcinomas (UCs) were immunohistochemically investigated with antibodies against cytokeratins (CKs), vimentin, p53 protein, c-erbB-2 protein and CEA. The diagnoses were based on the findings of conventional histopathology, immunohistochemistry and electron microscopy. CKs8, 18 and 19 were the CKs most frequently present in these tumors, in 61%, 61% and 82% of the cases, respectively. Nine of the 28 (32%) UCs were CKs5/6 positive. Expression of CK20 was found in three (11%) cases. Four UCs were sub-type Cks negative, but one of them was confirmed AE1/AE3 positive. P53 protein overexpression was found in nine (32%) cases. One of the patients with p53 protein positive tumors has been alive for 174 months. Nine (32%) UCs expressed vimentin, which included all of the three thyroid UCs. Comparing with our previous study of squamous cell carcinomas, we found that vimentin and CK18 are more frequently expressed in UCs. The overexpression of p53 protein is similar in the two groups of carcinomas and thus, p53 protein is not a differentiation marker in these tumors. Finally, we recommend the use of a CK "cocktail of antibodies" in the diagnosis of UCs.

Adolescent↗

PubMedDate not supplied

Laminin production and fibronectin immunoreactivity in breast carcinomas.

Eighty-nine cases of primary breast carcinoma were evaluated immunohistochemically for basement membrane laminin and fibronectin (FN). 58 of the cases were also examined by transmission electron microscopy (TEM). Intraductal carcinomas were all positive for laminin and FN and by electron microscopy a continuous BM was found in all of them. Among invasive tumors, immunoreactivity for laminin was expressed in 31% of cases and FN in 66%, whereas TEM revealed BM in only 4 out of 52 (8%) studied cases. Tumors measuring 10 mm or less were more often laminin-positive and FN-negative than larger tumors. There was a tendency for lymph node negative tumors to express laminin more often, but there was no relation between lymph node status and FN. Laminin immunostaining proved to be very useful in identifying vascular invasion. The laminin and FN immunoreactivity showed no significant correlation with overall survival and disease-free survival (DFS) of the breast cancer patients. DFS for cases with laminin positive tumors was 50% and for laminin negative tumors 46.8%. For cases with tumors immunoreactive for FN, DFS was 50%, and for tumors lacking FN 43.5%.

Basement Membrane↗

PubMedDate not supplied

Lack of expression of c-erbB-2 oncoprotein in human esophageal squamous cell carcinomas.

Fifty-one cases of esophageal squamous cell carcinoma were immunohistochemically investigated with monoclonal c-erbB 2 oncoprotein antibody. No tumor showed plasma membrane immunostaining for c-erbB-2 protein. Occasionally, unspecific cytoplasmic staining was found in minor tumor cell populations. The present results show that c-erbB-2 oncoprotein is not overexpressed in esophageal squamous cell carcinomas and does not play a central role in the tumorigenesis.

Animals↗

PubMedDate not supplied

Expression of stromelysin-3 in medullary carcinoma of the breast.

Matrix metalloproteinases are belived to play a central role in the invasion and metastasis of human cancers by mediating the degration of extracellular matrix components. Expression of stromelysin-3 (ST3), a new member of matrix metalloproteinase family, was investigated by in situ hybridization in 32 tissue samples of medullary carcinoma of the breast. Eighty-four per cent of the cases showed ST3 gene expression in stromal cells adjacent to tumor cells. Therefore, expression of ST3 in stromal cells may be expected to play a significant role in the destruction of extracellular matrix and invasion of medullary carcinoma of the breast.

Adult↗