Biomedical subjects

P Lipponen

Publications and source records attributed to P Lipponen.

125 records · Page 7Linked to original sources

PubMedDate not supplied

Expression of c-myc proteins in breast cancer as related to established prognostic factors and survival.

The expression of c-myc proteins was analysed immunohistochemically in a series of 206 breast carcinomas with special focus on established prognostic factors and patient survival. Nuclear expression of c-myc proteins was detected in 12% of carcinomas, and it was related to the lack of estrogen receptors (p = 0.05). Cytoplasmic expression of c-myc was present in 95% of the tumours. Expression of cytoplasmic c-myc at the invasive margin was related to tumour grade (p = 0.0013), low mitotic index (p = 0.0002) and low S phase fraction (p = 0.026), and weakly associated with distant metastasis at diagnosis (p = 0.06) and to a high proportion of intraductal growth (p = 0.08). Long recurrence-free survival of the patients was related to strong cytoplasmic expression of c-myc at the invasive margin in the entire series (p = 0.0049) and in axillary lymph node-negative (ANN) (p = 0.0028) tumours. Cytoplasmic c-myc expression in the central areas of the tumour predicted metastasis at diagnosis (p = 0.002), non-ductal type of growth (p = 0.018) and low mitotic index (p = 0.005). Expression of c-myc in the stroma was related to the lack of estrogen receptors (p = 0.02) and to high S phase fraction (p = 0.01). The results show that overexpression of c-myc is involved in a highly complex manner with the early stages of breast cancer development, but it shows hardly any independent prognostic value over standard prognostic factors in clinical disease.

Adult↗

PubMedDate not supplied

Expression of C-242 antigen in pancreatic ductal adenocarcinoma.

This investigation was undertaken in order to analyse the expression of tumor associated antigen CA 242 in normal pancreas, in chronic pancreatitis and in pancreatic ductal adenocarcinoma, and to find out if the expression of CA 242 in carcinoma specimens would have prognostic significance. The expression of CA 242 was examined in the tissue specimens by the avidin-biotin-immunoperoxidase technique. According to our results, normal pancreas showed no or only weak staining for CA 242, whereas chronic pancreatitis samples stained somewhat intensely. Five out of 39 adenocarcinomas were negative for CA 242, 5 showed weak staining and 29 showed intermediate or intense staining. Positive staining was found mostly in the ductal cells as well as in intraluminal contents. We found no statistically significant difference of CA 242 expression between different grades. The staining intensity and survival had no clear statistical correlation but all carcinoma patients whose survival time was more than twelve months showed an intense staining for CA 242. The results suggests that the expression of tumour associated antigen CA 242 may have prognostic significance in pancreatic adenocarcinoma.

Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

Results of the primary treatment in T1-3M0 prostatic adenocarcinoma are dependent on tumour biology.

The results of the primary treatment were analysed in relation to biological prognostic factors in a series of 215 males with T1-3M0 prostatic adenocarcinoma. T-category, Gleason score and DNA ploidy were significantly related to progression-free survival and overall survival. Incidental tumours usually had a favorable prognosis, 86% of them being diploid, whereas the incidental aneuploid tumours (14%) ran an unfavorable course. In clinically malignant prostates (TPR), neither Gleason score nor DNA ploidy had prognostic significance. The treatment had prognostic significance only in diploid tumours or in tumours with Gleason score value < or = 7, while aneuploid tumours or tumours with Gleason score value > 7 always had unfavorable prognosis irrespective of treatment. Tumours treated by radical prostatectomy or by radical radiation treatment were associated with a favorable prognosis, as contrasted to the tumours treated by endocrine treatment or those followed-up only, which had a high rate of mortality. Transurethral resection was weakly related to increased risk of death from prostatic adenocarcinoma, although the basic mechanisms behind this observation remain to be explained.

Adenocarcinoma↗

PubMedDate not supplied

Tumor vascularity and basement membrane structure as prognostic factors in T1-2MO prostatic adenocarcinoma.

The basement membrane (BM) structure and vascular density (VD) were analysed using collagen IV immunostaining in a series of 88 T1-2MO prostatic adenocarcinomas. The results were correlated with the established prognostic factors and patient survival based on a follow-up of > 11 years. Prostatic cancer cells retained their capacity to synthesize BM components, although defects in the BM structures were associated with T2 category and high Gleason score. Progression of the tumours was related to the defects in BM continuity, and defective BMs were also a sign of poor outcome. High grade tumours were occupied by dense vascular network and dense VD was a sign of a poor outcome. Gleason score was a significant predictor of progression and patient survival, as was the T-category. Multivariate analysis of the prognostic factors indicated that Gleason score included all the available independent prognostic information. The results show that all prostatic adenocarcinomas continue to synthesize BM components, although the structure and continuity is disturbed in poorly differentiated tumours. A rich vascular network is a sign of highly malignant phenotype in prostatic adenocarcinoma. However, an assessment of the BM and VD is of limited independent prognostic value.

Adenocarcinoma↗

PubMedDate not supplied

Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in axillary lymph node negative breast cancer.

The fraction of nuclei positive for proliferating cell nuclear antigen (PCNA) was determined in 205 axillary lymph node negative (pN-) breast carcinoma. The results were related to established prognostic factors and prognosis during the mean follow-up period of 11 years. The maximum fraction of PCNA-positive nuclei (PCNAmax), the average fraction of positive nuclei (PCNAtot) and the number of intensively stained nuclei/microscope field (PCNAcount) were significantly related to histological grade (p < 0.001), DNA Ploidy (p < 0.022), S phase fraction (p < 0.003) and mitotic index (p < 0.003). PCNAmax (p = 0.020) and PCNAcount (p < 0.003) predicted recurrence-free survival in univariate analysis whereas tumour diameter (p < 0.001) was an independent predictor in a multivariate analysis. In univariate survival analysis PCNAtot (p < 0.0178), PCNAmax (p = 0.0054) and PCNAcount (p < 0.001) predicted survival and in multivariate analysis PCNAcount (p = 0.006), patient age (p = 0.040) and tumour diameter (p = 0.042) were related independently to survival. The results indicate that PCNA immunolabeling has prognostic value in local breast cancer.

Adult↗

PubMedDate not supplied

Expression of tumour associated antigens 12H12, 2E11, 7A9, CEA and DF3 in human breast cancer.

Expression of tumour associated antigens 12H12, 2E11, 7A9, CEA and DF3 was determined immunohistochemically in paraffin embedded biopsy specimens from 42 breast carcinomas. The mean (SD) of staining index (I) for 12H12 was 0.95(0.94), for 2E11 1.30(0.99), for FA9 1.11(0.92), for CEA 0.03(0.1) and for DF3 1.32(0.93). Of the 42 carcinomas, 3 (7.1%) were totally negative for 12H12, 3/42 (7.1%) for 2E11, 6/42 (14.3%) for 7A9, 34/42 (81%) for CEA and 6/45 (13.3%) for DF3. The 12H12 positivity was related significantly to axillary lymph node status (r = 0.41, p < 0.01), expression of 7A9 (r = 0.71, p < 0.001), expression of 2E11 (r = 0.76, p < 0.001), expression of DF3 (r = 0.40, p < 0.01) and TPA serum level (r = 0.41, p < 0.01). The 2E11 positivity was related to axillary lymph node status (r = 0.43, p < 0.01), expression of 7A9 (r = 0.95, p < 0.001) and 12H12 (r = 0.76, p < 0.001). The 7A9 positivity was related to axillary lymph node status (r = 0.44, p < 0.01), expression of 7A9 (r = 0.71, p < 0.001), 12H12 (r = 0.71, p < 0.001) and 2E11 (r = 0.95, p < 0.001). The DF3 positivity was significantly related to expression of 12H12 (r = 0.40, p < 0.01). The CEA positivity was not significantly related to any of the tested variables. The results suggest that antigens 12H12, 2E11 and 7A9 should be subject to further analysis in breast cancer research. Particularly, they may be helpful in separating benign breast lesions from the more malignant ones. Secondly, the relationship between high expression of the antigens and axillary lymph node status suggests that these antigens may have also prognostic value.

Antigens, Neoplasm↗

PubMedDate not supplied

Mast cells in breast cancer.

The number of stromal mast cells was counted in 187 breast carcinomas. The number of mast cells/mm2 of tumour stroma was studied in relation to clinical, histological and quantitative prognostic factors and survival. A high number of mast cells in tumour stroma was significantly related to low S phase fraction (p = 0.001), DNA diploidy (p = 0.028), high proportion of intraductal growth (p = 0.003) and high degree of tubule formation (p = 0.044). Large tumours showed a lower number of mast cells in stroma (p = 0.08). A non-significant trend was found between mast cell count and axillary lymph node status, sex steroid receptor content, histological type, morphometric nuclear factors and mitotic frequency. In survival analysis a high mast cell count (over 10 g per mm2 of tumour stroma) was related to a favorable prognosis (p = 0.04). The present results confirm previous results in that changes in mast cell count are related to histopathological characteristics and clinical outcome in breast cancer.

Adult↗

PubMedDate not supplied

Mitotic activity index, volume corrected mitotic index and human papilloma-virus suggestive morphology are not prognostic factors in carcinoma of the oesophagus.

Radiation treatment, endoscopic dilatations and laser treatment offer an alternative to surgery as palliation in oesophageal cancer, and therefore it is essential to assess the prognostic factors preoperatively in order to select the treatment individually. Mitotic activity index (MAI), volume corrected mitotic index (M/V-index) and histologic evidence for human papillomavirus (HPV) involvement together with other prognostic factors were studied in 61 patients with oesophageal squamous cell carcinomas. No patient was lost from follow-up and 18% of patients were alive at the end of follow-up. Evidence for HPV involvement was found in 11 (18%) of 61 patients, which was significantly (p < 0.001) less than in a previous series of Chinese patients. Histological grade (p = 0.025), lymph node status (p = 0.002), presence of distant metastasis (p = 0.004), surgical resection (p = 0.03) and nuclear pleomorphism (p = 0.04) were significant independent prognostic factors in univariate analysis. In multivariate analysis, the length of the tumour (p = 0.0002) as well as its histological grade (p = 0.0001) significantly predicted the patient survival. Surgical resection was almost included into the model (p = 0.11). On the other hand, MAI, M/V-index or HPV histology did not reach statistical significance as prognostic factors.

Aged↗

PubMedDate not supplied

Ag-NORs related to flow cytometry, morphometry and prognosis in patients with pancreatic cancer.

The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag-NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and that the number of Ag-NORs predicts survival.

Adenocarcinoma↗

PubMedDate not supplied

Prognostic evaluation of DNA flow cytometry and histo-morphological criteria in renal cell carcinoma.

Clinical, histological and flow cytometric data (DNA content, S phase fraction) were related to clinical behaviour in 124 patients with renal cell carcinoma followed up for more than nine years. 69% of the tumours were diploid and 31% were aneuploid. The S phase fraction (SPF) ranged between 0.5% and 17.2% and the mean (s.e.) was 3.8 (0.3)%. The SPF was higher in aneuploid than in diploid tumours [mean, s.e., 2.6 (0.2)% vs. 6.4 (0.6)%, p < 0.001]. DNA ploidy was not related to any of the analysed features, while S phase was related to nuclear grade (p < 0.001), combined nuclear grade (p = 0.0025) and node metastasis at diagnosis (p = 0.036). In a multivariate analysis, the recurrence-free survival of M0 tumours was independently predicted by combined nuclear grade (p < 0.001), M/V index (p = 0.007), T-category (p = 0.011) and location (left/right) (p = 0.022). Survival in the entire cohort was independently related to T-category (p < 0.001), M/V index (p = 0.001) and DNA ploidy (p = 0.050). Survival of M0 tumours was independently related to M/V index (p < 0.001), DNA ploidy (p = 0.005) and T-category (p = 0.003). DNA aneuploidy was related to favorable disease outcome both in univariate and multivariate analysis in the entire series and in all the subanalyses. The results suggest that genomic instability in aneuploid cells may reduce their capacity to resist immunological host response or aneuploid tumours may be more sensitive to treatment.

Adult↗

PubMedDate not supplied

Prognostic significance of TGF-beta 1 and TGF-beta 2 expressions in female breast cancer.

A series of 273 breast cancer biopsies were analysed immunohistochemically for the expression of transforming growth factor beta-1 (TGF-beta 1) and beta-2 (TGF-beta 2) as related to standard prognostic factors and patient survival. TGF-beta 1 expression was found in 160/273 (59%) and TGF-2 in 110/273 (40%) of tumour specimens. Both isoforms were expressed in 89/273 (33%) of cases. TGF-beta 1 alone was expressed in 71/273 (26%) of cases and TGF-beta 2 alone was expressed in 19/273 (7%) of cases. The expression of TGF-beta 1 and TGF-beta 2 were both uniformly related to some other favourable prognostic factors. The expression of TGF-beta 2 without the expression of TGF-1 was significantly related to favourable disease outcome. The result of this study is in agreement with the previous studies of TGF-beta mRNA and also in vitro studies, but the result differs from some previous immunohistological studies. This study also suggests that the expression of TGF beta may have independent prognostic value over the expression of TGF-beta 1.

Breast Neoplasms↗

PubMedDate not supplied

Expression of epidermal growth factor receptor (EGFR) in breast cancer as related to clinical, prognostic and cytometric factors.

A series of 213 female breast carcinomas were analysed immunohistochemically for the expression of epidermal growth factor receptor (EGFR), with special emphasis on its possible prognostic significance. A total of 114/213 tumors (53.5%) were EGFR positive. EGFR was almost exclusively expressed in the cytoplasm of the cancer cells, but in a few cases, the cell membranes showed EGFR positive staining as well. EGFR expression was related to the histological grade of the tumours in that a linear decrease of the staining was found in parallel with the decreasing tumour differentation (P = 0.024). On the other hand, axillary lymph node status (P = 0.95), histological type (P = 0.60), tumor size (P = 0.87), DNA-index (P = 0.56), S-phase (P = 0.80), mitotic index (P = 0.72), or estrogen (ER) and progesterone receptor (PR) content (P = 0.45) did not show any statistical correlation with the EGFR expression. EGFR positivity as an independent factor, had little (if any) effect on the patients prognosis. Tumor size (P = 0.004), axillary lymph node involvement (P = 0.024) and PR positivity (P = 0.008) were the single most significant prognostic factors in multivariate survival analysis. The results indicate that, in clinical breast cancer, immunohistochemical assessment of EGFR provides no prognostic information additional to the well established prognostic factors.

Adult↗

PubMedDate not supplied

A prognostic score for prostatic adenocarcinoma based on clinical, histological, biochemical and cytometric data from the primary tumour.

The aim of this study was to create a multivariate prognostic score for prostatic adenocarcinoma. A retrospective analysis of clinical, histological and cytometric prognostic factors in 325 cases of prostatic adenocarcinoma followed up on average over 13 years was performed. A multivariate prognostic score was built by using the independent prognostic factors. M-category, T-category, Gleason score and patient age were independent prognostic factors in the entire cohort. In MO tumors T-category, density of tumor infiltrating lymphocytes, the presence of apoptotic cells, and patient age were independent prognostic factors. In T1-2MO tumors the density of tumour infiltrating lymphocytes, mitotic index, standard deviation of maximum nuclear diameter and the serum level of acidic phosphatase were independent prognostic factors. By combining the coefficients of the regression model, a prognostic score was built for each of the tumour categories. The subsequent survival analysis based on the prognostic score indicated that it is a highly significant prognostic factor superior to individual prognostic parameters. The results show that the combination of prognostic data is a valuable tool in assessing the correct prognostic category for prostatic adenocarcinoma.

Adenocarcinoma↗

PubMedDate not supplied

Comparison of classic and quantitative prognostic factors in colorectal cancer.

Despite the many pathologic and clinical variables shown to influence survival rates in patients with colorectal cancer, the prediction of outcome after curative resection is still not completely reliable. Dukes-classification has been historically the strongest prognostic indicator and the most frequently employed method. In this study our aim was to search for significant independent histological and morphometric factors that could possibly be used in predicting the outcome of different stages of colorectal cancer. We analysed the clinical follow-up data of 308 patients with colorectal adenocarcinoma (followed-up for a mean of 14.4 years). The clinical findings were correlated to histological and morphometric factors to establish their value as predictors of colorectal adenocarcinoma Clinical, histological and morphometric factors were significantly interrelated. The large invasive tumours had larger nuclei, a larger variation in nuclear size, and they were also rapidly proliferating. In univariate survival analysis Dukes, the mean nuclear area (NA), standard deviation of nuclear area (SDNA), nuclear perimetry (PE) and the mean of the longest nuclear axis (Dmax) were the most important predictors of recurrence-free survival (RFS). TNM-categories, Dukes, histological grade and all the quantitative variables were significant predictors of cancer related survival. In a multivariate analysis of Tl-4N0-3M0 tumours (n = 164) N-category, nuclear area and the vear of operation and in local tumours (Tl-2N0M0) (n = 70) Dmax and Dukes predicted RFS. Important determinants of survival in all 269 cases were M-category. Dukes and Dmax and in local tumours (Tl-2N0M0) (n = 67) Dmax. These results indicate that although an accurate prognostic evaluation of colorectal carcinomas can be based on TNM- and Dukes-classification, nuclear morphometry can give additional prognostic information.

Adult↗

PubMedDate not supplied

Cell proliferation in aortic, mammary artery and saphenous vein biopsies in patients subjected to open heart surgery.

BACKGROUND: Stenosis of venous vascular grafts is a common phenomenon after coronary by-pass surgery and the factors related to stenosis are not completely understood. Cell proliferation in vascular channels is one of the features related to occlusion. This study is a prospective clinicopathological study of the relationship between cell proliferation and clinical factors in patients suffering from atherosclerotic heart disease. Materials. The expression of cell proliferation related protein Ki-67 was analyzed in samples obtained from aortic wall, internal mammary artery, and saphenous vein in 96 patients subjected to open heart surgery. METHODS: The expression of Ki-67 in vascular channel intima and media was analyzed by immunohistochemical techniques. The results of Ki-67 immunolabelling were compared to clinical features and to the medical therapy of the patients. RESULTS: Cell proliferation was higher in males than in females in the aortic wall (p = 0.05). The expression of Ki-67 was significantly higher (p = 0.004) in venous intima in patients with insulin-dependent diabetes than in patients with non-insulin dependent diabetes or with no diabetes. CONCLUSIONS: The results show that variations in cell proliferation rates in vessel walls may be related to the potential risk of stenosis of vascular grafts particularly in patients with insulin-dependent diabetes mellitus.

Adult↗

PubMedDate not supplied

Bcl-2 and p53 protein expression in aortic, mammary artery and saphenous vein biopsies in patients subjected to open heart surgery.

BACKGROUND: Stenosis of vascular grafts is a common phenomenon after coronary by-pass surgery and factors favoring stenosis are incompletely understood. The present study is a prospective clinicopathological study on the relationship between factors controlling cell proliferation (p53) and programmed cell death (bcl-2) in patients suffering from atherosclerotic heart diseases. MATERIALS: The expression of p53 and bcl-2 proteins was analyzed in samples obtained from the aortic wall, internal mammary artery, and saphenous veins in 96 patients subjected to open heart surgery. METHODS: The expression of p53 and bcl-2 proteins in vascular channel intima and media was analyzed by immunohistochemistry. RESULTS: The expression of bcl-2 was more common in males than in females (p = 0.05). The expression of bcl-2 was significantly more common (p = 0.004) in venous intima in patients with insulin-dependent diabetes than in patients with non-insulin dependent diabetes or with no diabetes. Expression of p53 was related to insulin-dependent diabetes in venous intima with a borderline significance (p = 0.08). CONCLUSIONS: The results show that bcl-2 and p53 are expressed in vessel walls and may be related to potential risk of stenosis of vascular grafts particularly in patients with insulin-dependent diabetes mellitus.

Adult↗

PubMedDate not supplied

Clinical contribution of bcl-2, p53 and Ki-67 proteins in pancreatic ductal adenocarcinoma.

The expression of apoptosis suppressing protein bcl-2, tumour-suppressor protein p53, and proliferation marker Ki-67 and their possible prognostic value were analysed in pancreatic ductal adenocarcinoma. Fifty-two % (34/64) of the samples were positive for bcl-2 and immunostaining were mainly localized in the cytoplasm of tumour cells. Bcl-2 expression was not related to tumour grade, DNA ploidy or S-phase fraction or to any clinical parameters. In univariate analysis bcl-2 expression predicted favourable outcome (p = 0.008). Positive nuclear staining for p53 was found in 40% (24/59) of samples and 80% (60/74) of the tumours were positive for Ki-67. p53 and Ki-67 expressions were not related to patient survival. According to our results, bcl-2 expression seems to be a predictor of disease outcome and may have some clinical value in human pancreatic cancer.

Aged↗