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Biomedical subjects

Johan Lundin

Publications and source records attributed to Johan Lundin.

At least 19 recordsLinked to original sources
PubMed2006

Ki-67, p53, ER receptors, ploidy and S phase as long-term prognostic factors in T1 node-negative breast cancer.

BACKGROUND: The aim of the present study was to evaluate a series of biomarkers with regard to long-term prognostic value in patients with T1 (< or =2 cm) node-negative breast cancer. METHOD: The prognostic value of Ki-67, p53, oestrogen receptor (ER) immunohistochemical labelling, flow-cytometric S phase fraction and ploidy was evaluated in 212 patients with pT1N0M0 breast cancer. The median follow-up time was 15.9 years (range 0.2-27.2 years). RESULTS: In an analysis of breast cancer-specific survival up to 5 years, high Ki-67 (> or =10%; p = 0.002), high p53 (> or =20%; p = 0.01), negative ER (<30%; p = 0.01) as well as aneuploidy of the tumour (p = 0.02) were significant prognostic factors. When the follow-up was extended to 10 years, only Ki-67 (p = 0.03) was significantly associated with outcome and beyond 15 years none of the studied markers provided significant prognostic information when analyzed separately. There was a weak but significant difference in long-term survival when patients with a combination of high Ki-67 (> or =10%), high SPF (>3%) and high p53 (> or =20%) were compared to patients with other combinations (p = 0.03). CONCLUSION: According to the results of our series, it seems that several prognostic markers which are associated with short-term survival (< or =5 years) in pT1N0M0 breast cancer may not be significant predictors of long-term (>15 years) breast cancer-specific survival.

Adult↗
PubMed2006

Generalisability of survival estimates for patients with breast cancer--a comparison across two population-based series.

The purpose of the study was to analyse the generalisability and geographic transportability of survival estimates produced by commonly used prognostic factors. We compared the influence of tumour size, histologic grade, axillary nodal status, oestrogen and progesterone receptor contents, age at diagnosis and two prognostication schemes (the Nottingham Prognostic Index and St. Gallen criteria) in two nationwide cohorts of patients diagnosed with breast cancer in 1991-2, the FinProg (n=2923, Finland) and the SEER series (n=43,249, the United States (US)). Eight-year estimates of breast cancer-specific (84% versus 80%), relative (86% versus 83%), and overall (70% versus 69%) survival were slightly more favourable in the SEER than in the FinProg series, respectively. Despite differences in demographic variables and the frequency of use of adjuvant therapies and mammography screening between the series, the prognostic factors examined produced close to overlapping survival curves with similar shapes. The results suggest that quantitative survival estimates based on frequently used prognostic factors and prognostication schemes are generalisable and transportable between large, unselected cohorts of breast cancer patients.

Adult↗
PubMed2006

Virtual microscopy in prostate histopathology: simultaneous viewing of biopsies stained sequentially with hematoxylin and eosin, and alpha-methylacyl-coenzyme A racemase/p63 immunohistochemistry.

PURPOSE: Histopathological diagnosis of small focus carcinomas in prostatic needle biopsies is often assisted by IHC. To make a definitive diagnosis the pathologist must compare IHC findings with hematoxylin and eosin stained tissue morphology. We introduce what is to our knowledge a new application of virtual microscopy, in which hematoxylin and eosin, and IHC stains done sequentially on the same microscope slide can be simultaneously displayed and compared on a computer screen. MATERIALS AND METHODS: A total of 30 hematoxylin and eosin stained prostatic needle biopsies were scanned with a computer controlled microscope. The slides were destained and then immunostained with a cocktail of AMACR and p63 antibodies, which labels the nuclei of nonmalignant basal cells (p63) and the cytoplasm of neoplastic glandular cells suspicious for malignancy (AMACR). The slides were then scanned again and the pairs of virtual slides were aligned for synchronized viewing. RESULTS: The presented technique was found helpful when suspicious lesions were small and when examining the immunoprofile of specimens was warranted, in addition to examining hematoxylin and eosin stained tissue morphology. The usefulness of our approach based on virtual microscopy can be evaluated on the website , which also serves as an educational tool for self-learning the correlation between hematoxylin and eosin stained tissue morphology, and AMACR/p63 IHC in prostate biopsies. CONCLUSIONS: The technology for simultaneously viewing sequentially hematoxylin and eosin and IHC stained prostate biopsies can be readily used for educational purposes, as exemplified by our website, and along with the availability of rapid virtual slide scanners it can also be used for clinical diagnostics.

Biopsy, Needle↗
PubMed2005

Cyclooxygenase-2 is an independent prognostic factor in gastric cancer and its expression is regulated by the messenger RNA stability factor HuR.

PURPOSE: Cyclooxygenase-2 (COX-2) promotes carcinogenesis and its expression associates with clinicopathologic characteristics in gastric cancer. HuR is an mRNA binding protein that controls the stability of certain transcripts including COX-2. We evaluated the prognostic significance of COX-2 and HuR expressions in gastric cancer and whether there exists a link between HuR and COX-2 expressions. EXPERIMENTAL DESIGN: The study included 342 consecutive patients with histologically confirmed gastric adenocarcinoma, of whom 321 patients had tissue specimens available for COX-2 and 316 for HuR immunohistochemistry. Specimens were stained by COX-2- and HuR-specific monoclonal antibodies and scored by two independent observers. Correlation to clinical data and survival was assessed. TMK-1 gastric adenocarcinoma cells were treated with small interfering RNA against HuR and expressions of HuR and COX-2 were detected by immunofluorescence and Western blot analysis. RESULTS: Patients with low COX-2 expression had a cumulative 5-year survival of 53% and those with high COX-2 expression had 16% (P < 0.0001). In multivariate analysis, COX-2 was an independent prognostic factor (P = 0.003). Cytoplasmic HuR expression was associated with high COX-2 expression (P < 0.0001) and with reduced survival (P = 0.004) whereas nuclear positivity for HuR was not. When TMK-1 cells were treated with HuR small interfering RNA, expressions of HuR and COX-2 were reduced. CONCLUSIONS: High COX-2 is an independent prognostic factor in gastric cancer. Cytoplasmic expression of HuR associates with high COX-2 expression and with reduced survival, and tissue culture experiments show that HuR can regulate expression of COX-2 in gastric cancer cells.

Adenocarcinoma↗
PubMed2005

Down-regulated xanthine oxidoreductase is a feature of aggressive breast cancer.

PURPOSE: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA, and high-energy phosphates and also plays a role in milk lipid globule secretion. Given the strong and regulated expression of XOR in normal breast epithelium, and the previously shown alterations of its expression in experimental tumorigenesis, we hypothesized that XOR may be differentially expressed in breast cancer. EXPERIMENTAL DESIGN: XOR expression was analyzed by immunohistochemistry in tissue microarray specimens of 1,262 breast cancer patients with a median follow-up of 9.5 years. RESULTS: Expression of XOR was moderately decreased in 50% and undetectable in another 7% of the tumors. Decreased XOR expression was associated with poor histologic grade of differentiation, ductal and lobular histologic types, large tumor size, high number of positive axillary lymph nodes, and high cyclooxygenase-2 expression, but not with estrogen or progesterone receptor status, Ki-67, p53, or ERBB2 amplification. Absence of XOR expression was associated with unfavorable outcome, and patients with no XOR expression had more than twice the risk of distant recurrence as compared with those with a moderately decreased or normal expression (hazard ratio, 2.21; P < 0.0001). This was also true in patients with node-negative disease (hazard ratio, 2.75; P < 0.0001) as well as in patients with small (< or = 1 cm) tumors (hazard ratio, 3.09; P = 0.027). In a multivariate survival analysis, negative XOR emerged as an independent prognostic factor both in the entire series (P = 0.01) and among patients with node-negative disease (P = 0.0009). CONCLUSION: Loss of XOR identifies breast cancer patients with unfavorable prognosis.

Breast↗
PubMed2005

Syndecan-1 expression--a novel prognostic marker in pancreatic cancer.

OBJECTIVE: Syndecan-1 is a transmembrane receptor that participates in cell-cell and cell-matrix interactions, cell proliferation and cell migration. Expression of syndecan-1 is downregulated in many cancers, but in pancreatic ductal adenocarcinoma it is upregulated. METHOD: We studied the immunohistochemical expression of syndecan-1 in 144 pancreatic adenocarcinomas and evaluated the prognostic value of syndecan-1 expression. Formalin-fixed, paraffin-embedded specimens were stained with mouse monoclonal antibody B-B4 against human syndecan-1. The epithelial and stromal staining was separately evaluated and compared with patient survival, clinical stage and histological grade. RESULT: Epithelial immunoreactivity was observed in most of the pancreatic carcinoma samples: in 70 (49%) of the samples the epithelial staining was weak, in 48 (33%) moderate, in 18 (12%) strong and in only 8 (6%) of the samples the epithelial staining was negative. Stromal staining was weak in 24 (17%), moderate in 31 (22%), strong in 11 (8%) and negative in 78 (54%) of the pancreatic carcinoma samples. Lack of stromal expression predicted a better prognosis (p = 0.002; HR 1.7) and it was independent of stage (p = 0.01; HR = 1.5) and grade (p = 0.0004; HR 2.1) in multivariate analysis. Epithelial expression predicted better prognosis for patients that underwent surgery for cure (n = 94, p = 0.03). CONCLUSION: Stromal syndecan-1 expression is an independent prognostic marker in pancreatic cancer, whereas epithelial syndecan-1 expression predicts better prognosis only in resectable disease.

Acute Disease↗
PubMed2005

Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma.

HuR is a ubiquitously expressed mRNA-binding protein. Intracellular localization of HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm it can stabilize certain transcripts. Because nucleocytoplasmic translocation of HuR is necessary for its activity, it was hypothesized that cytoplasmic HuR expression in cancer cells could be a prognostic marker. To test the significance of HuR in carcinogenesis of the breast, we have investigated HuR expression in a mouse mammary gland tumor model and from 133 invasive ductal breast carcinoma specimens. HuR expression was elevated in the cyclooxygenase-2 transgene-induced mouse mammary tumors, and its expression was predominantly cytoplasmic in the tumor cells. In the human carcinoma samples, high cytoplasmic immunoreactivity for HuR was found in 29% (38 of 133) of the cases. Cytoplasmic HuR expression associated with high grade (P = 0.0050) and tumor size over 2 cm (P = 0.0082). Five-year distant disease-free survival rate was 42% [95% confidence interval (95% CI), 26-58] in cytoplasm-high category and 84% (95% CI, 76-91) in cytoplasm-negative or -low category (P < 0.0001), and high cytoplasmic expression of HuR was an independent prognostic factor in a Cox multivariate model (relative risk 2.07; 95% CI, 1.05-4.07). Moreover, high cytoplasmic HuR immunopositivity was significantly associated with poor outcome in the subgroup of node-negative breast cancer in a univariate analysis (P < 0.0007). Our results show that high cytoplasmic HuR expression is associated with a poor histologic differentiation, large tumor size, and poor survival in ductal breast carcinoma. Thus, HuR is the first mRNA stability protein of which expression associates with poor outcome in breast cancer.

Animals↗
PubMed2005

Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells.

ErbB1 and ErbB2 receptors are well-characterized targets for anticancer drugs, but the clinical relevance of the related ErbB4 receptor is unknown. Here, we have assessed the clinical significance of the proteolytically cleavable ErbB4 isoforms in breast cancer patients and investigated their functions in vitro. The expression of transcripts encoding the cleavable ErbB4 isoforms associated with estrogen receptor-alpha (ER) expression (P < 0.001) and a high histologic grade of differentiation (P </= 0.002) in real-time reverse transcription-PCR analysis of 62 breast cancer samples. Despite high ErbB4 mRNA expression levels in a subset of samples, ErbB4 gene amplification was not observed. High ErbB4 protein expression levels, as assessed by immunohistochemistry, associated with a favorable outcome in ER-positive cases from a series of 458 breast cancer patients (P = 0.01), whereas no association between ErbB4 expression and survival was found among women with ER-negative cancer (P = 0.86). However, nuclear ErbB4 immunoreactivity was associated with poor survival as compared with women whose cancer had membranous ErbB4 staining (P = 0.04). In vitro, overexpression of a cleavable ErbB4 isoform in ER-positive breast cancer cells resulted in translocation of a proteolytically released intracellular ErbB4 receptor fragment into the nucleus, as well as, enhanced proliferation, anchorage-independent growth, and estrogen response element-mediated transcriptional activity. These results suggest that the association of ErbB4 expression with clinical outcome is dependent on the subcellular localization of ErbB4 and that a proteinase-cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances ER-mediated gene transcription.

Alternative Splicing↗
PubMed2005

Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer.

Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) associates with reduced survival in human breast cancer. COX-2 may be directly involved with mammary carcinogenesis, since expression of COX-2 is sufficient for formation of breast tumors in transgenic mice, and COX-2 selective inhibitors can suppress tumorigenesis in rodent models of breast cancer. MMP-2 is an extracellular matrix degrading proteolytic enzyme that bas been linked to invasion and metastasis. A direct link between COX-2 and MMP-2 may exist, since inhibition of COX-2 activity can result in reduction of MMP-2 expression and activity. In this study we analyzed protein expression of COX-2 and MMP-2 in tissue array specimens of 278 invasive breast cancers by immunohistochemistry. Immunopositivity of these two markers was correlated with each other and with various clinicopathological parameters including survival. We found high COX-2 expression in 30% and high MMP-2 expression in 83% of the breast cancer specimens, and there was a positive association between the expression of these two factors (p = 0.003). It was especially evident that whenever COX-2 expression was high, MMP-2 expression was almost invariably high (95%). Furthermore, high expression of either COX-2 or MMP-2 associated with decreased disease specific survival when compared with the COX-2 or MPP-2 low group (p = 0.026 and p = 0.021, respectively). Taken together, our results indicate that expression of COX-2 protein is associated with expression of MMP-2 protein in human breast cancer and that both COX-2 and MMP-2 are markers of poor prognosis in breast cancer.

Biomarkers, Tumor↗
PubMed2005

Web-based virtual microscopy in teaching and standardizing Gleason grading.

Gleason grading forms the basis of prognostic and therapeutic assessment in prostatic carcinoma despite its subjective nature and substantial interobserver variation. The accuracy of Gleason grading can be improved by the use of educational tools such as reference images. However, conventional microscopy images are of limited educational value because it is neither possible to view the sample at different magnifications nor to navigate into different areas of the specimen. This limitation can be overcome by the use of virtual microscopy, which allows viewing entire digitized microscope slides. We created an interactive Web site ( www.webmicroscope.net/gleason ) featuring a comprehensive set of prostatic needle biopsies as virtual slides, which can be viewed with a standard Web browser (Internet Explorer or Netscape). To evaluate the validity of Web-based virtual microscopy for Gleason grading, an experienced uropathologist (TK) scored a series of 62 biopsies from the original glass slides and 6 weeks later from virtual slides on the Web site using an ordinary desktop computer. The intraobserver agreement was excellent, with identical Gleason scores found in 48 of the 62 cases ( kappa = 0.73). The 14 remaining scores differed only by 1 point on the Gleason scale (2-10). The virtual slides were viewed by 2 other uropathologists (PM and HH), with interobserver kappa coefficients ranging from 0.55 to 0.62, which is within the range of previously reported studies using glass slides. The 3 uropathologists' Gleason scores were included as reference scores on the Web site, which now serves as a publicly open platform for self-testing and learning of Gleason grading. We conclude that Web-based virtual microscopy is a promising new tool for teaching and standardizing Gleason grading.

Biopsy, Needle↗
PubMed2004

High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer.

PURPOSE: The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium-specific hyaluronan receptor, is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues. EXPERIMENTAL DESIGN: We investigated expression of LYVE-1 by immunohistochemistry in 180 unilateral, invasive ductal breast carcinomas and assessed the presence and density of lymph vessels within the tumor and at the tumor periphery. RESULTS: A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No substantial association was found between the number of LYVE-1-positive vessels and the number of CD31 or vascular endothelial growth factor receptor-3-positive vessels, or vascular endothelial growth factor-C expression. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P = 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% confidence interval, 46-70%) 5-year distant disease-free survival as compared with 74% (66-83%) among those with a low peritumoral lymph vessel density (P = 0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis. CONCLUSIONS: A high peritumoral lymph vessel density is associated with a poor outcome in ductal breast cancer.

Adult↗
PubMed2004

Risk for distant recurrence of breast cancer detected by mammography screening or other methods.

CONTEXT: Selection of systemic adjuvant therapies for women diagnosed as having breast cancer is based on risk estimations for cancer recurrence. In such estimations, tumors detected by mammography screening are considered to be associated with a similar risk of recurrence as tumors of similar size found by other methods. OBJECTIVE: To compare the risk of recurrence and survival among women with cancerous tumors detected by mammography screening compared with other methods (outside of screening). DESIGN, SETTING, AND PATIENTS: Retrospective study comparing clinical, histopathological, and biological features of cancerous tumors detected by mammography screening compared with tumors detected outside of screening. Women diagnosed as having breast cancer in 1991 or 1992 were identified from the Finnish Cancer Registry (n = 2842). The median follow-up time was 9.5 years. Cancer biological variables were analyzed from tumor tissue microarrays using immunohistochemistry or in situ hybridization and included ERBB2, TP53, and MK167 expression and ERBB2 amplification data. MAIN OUTCOME MEASURES: Univariate and multivariate analyses of potential risk factors for distant recurrence of breast cancer and 10-year survival. RESULTS: Of the 1983 women with unilateral invasive breast cancer, data on tumor diameter were available for 1918 women. Women with cancerous tumors detected by mammography screening had better estimated 10-year distant disease-free survival than women with tumors found outside of screening (tumor size of < or =10 mm [n = 386] 92% vs 85% [P =.04]; 11-20 mm [n = 808] 88% vs 76% [P<.001]; 21-30 mm [n = 409] 86% vs 63% [P =.008]; >30 mm [n = 315] 68% vs 50% [P =.12], respectively). In a Cox multivariate model that included cancer biological factors, the relative hazard ratio for distant recurrence among women with tumors detected outside of screening (HR, 1.90; 95% confidence interval, 1.15-3.11) was significantly higher than among women with tumors detected by mammography screening (P =.01). Breast cancer diagnosis by mammography screening was an independent prognostic variable reducing the relative HR for distant recurrence. This effect was equal to or greater than the effect of 1-cm decrease in tumor diameter (HR, 1.20; 95% confidence interval, 1.10-1.31). CONCLUSIONS: Cancerous tumors detected by mammography screening are associated with a better prognosis than tumors of similar size found outside of screening. The risk of distant metastases is overestimated for women diagnosed as having cancer by mammography screening unless the method of detection is taken into account in risk estimations.

Adult↗
PubMed2004

Prognostic value of syndecan-1 expression in breast cancer.

OBJECTIVE: Syndecan-1 is a cell surface heparan sulphate proteoglycan which participates in cell proliferation, cell migration and cell-matrix interactions. Epithelial syndecan-1 expression is reduced in several malignant tumours, but in breast and pancreatic cancer, increased expression has also been described. Loss of epithelial syndecan-1 has been associated with poor prognosis in some forms of cancer, but previous findings in breast cancer have been contradictory. The objective of this study was to evaluate the prognostic value of the immunohistochemical expression of syndecan-1 in a series of 200 patients with invasive breast cancer with a median follow-up of 17 years. METHODS: Formalin-fixed paraffin-embedded specimens were stained using a monoclonal antibody against syndecan-1. RESULTS: Syndecan-1 was expressed in the epithelium in 61% and in the stroma in 67% of the tumours. Epithelial syndecan-1 expression was associated with negative oestrogen receptor (ER) status (p < 0.01), and stromal syndecan-1 expression with positive ER status (p = 0.02). The breast cancer-specific 10-year overall survival for patients with epithelial syndecan-1 expression was 65%, compared with 82% for those with loss of epithelial expression (p = 0.02). Ten-year survival was 66% for those expressing stromal syndecan-1 and 83% for those lacking stromal expression (p = 0.15). Patients with both epithelial and stromal expression had a 10-year survival of only 56%, compared to 78% in patients with other expression pattern combinations (p < 0.002). In Cox multivariate analysis, only axillary involvement and tumour size were significant predictors of breast cancer-specific survival. CONCLUSION: Concomitant expression of syndecan-1 in both epithelium and stroma may be a predictor of unfavourable prognosis in breast cancer, and in contrast with previous studies, loss of epithelial syndecan-1 was associated with a more favourable prognosis.

Adult↗
PubMed2004

Validation of a Web-based prognostic system for breast cancer.

A website has been published which allows the user to enter information on prognostic factors for a patient with breast cancer, and instantly obtain a survival curve based on outcome data of prior cases with a matching prognostic factor profile. The source for the survival data is a Finnish nationwide series (the FinProg series) of 2,842 women diagnosed with breast cancer in 1991-2. The purpose of this study was to compare survival estimates based on the FinProg database, with estimates for breast cancer patients from the US, obtained from the SEER public-use database and the same time-period. Results show that a reasonable level of agreement between estimates can be reached, by the use of large, unselected databases, and that significantly different estimates were obtained in only 2 of 19 analyzed prognostic profiles. The current system could be used to share important knowledge on outcome between researchers and clinicians at different institutions, and be used in the decision-making process concerning treatment of patients with breast cancer.

Breast Neoplasms↗
PubMed2003

Ski-related novel protein N (SnoN), a negative controller of transforming growth factor-beta signaling, is a prognostic marker in estrogen receptor-positive breast carcinomas.

Transforming growth factor (TGF)-beta arrests the growth of breast epithelial cells, whereas breast cancer cells are highly resistant to its growth restrictive properties. To define causes for the defect in TGF-beta action, we present here the first in vivo analysis of Ski-related novel protein N (SnoN), a negative regulator of TGF-beta signaling, in human breast carcinomas. SnoN expression was analyzed by immunohistochemistry in a tissue microarray of 1122 breast carcinomas and 10 reduction mammoplasties. In the normal breast, SnoN was located predominantly in nuclei of large duct epithelial cells and the cytoplasm of terminal duct epithelial cells. Breast cancers displayed variances in both SnoN expression levels and subcellular localizations. High levels of cytoplasmic SnoN were more often observed in tumors of ductal histological type and associated with adverse prognostic features, such as lack of hormone receptors; high levels of p53, Ki-67, and cyclooxygenase-2; and amplifications of HER-2. High levels of nuclear SnoN were associated with lobular histology and favorable features, including presence of hormone receptors, low expression of p53 and Ki-67, and lack of HER-2 amplifications. Reduced expression of SnoN significantly correlated with longer distant disease-free survival in estrogen receptor-positive patients (P = 0.0027, relative risk = 3.27; 95% confidence interval = 1.44-7.41). The results suggest that the subcellular localization of SnoN may have clinical significance and that reduced expression of SnoN is associated with favorable outcome in estrogen receptor-positive breast cancer.

Adult↗
PubMed2003

Distinct subtypes of serous ovarian carcinoma identified by p53 determination.

OBJECTIVE: The overall prognosis of ovarian carcinoma is poor. However, the outcome of apparently similar cases is highly variable, and molecular markers that would predict disease outcome in a clinically useful manner are lacking. We investigated the value of p53 expression as a disease determinant in serous carcinoma, which is the most common type of ovarian carcinoma and has shown the highest frequency of p53 alterations. METHODS: Tissue microarray constructed of 522 serous ovarian carcinomas was examined immunohistochemically using DO-7 monoclonal antibody against p53 protein. The findings were correlated with overall and disease-free survival, response to therapy, and clinicopathological characteristics of the patients. RESULTS: Both excessive and completely negative p53 staining confered poor patient outcome and were considered aberrant p53 expression. Patients with aberrant p53 (59% of the carcinomas) showed 5-year overall survival of 26% (20-31%), whereas patients with normal p53 expression (41% of the carcinomas) showed 5-year overall survival of 79% (95% CI, 74-85%) (P < 0.0001). The association of aberrant p53 with poor prognosis was independent of clinicopathological parameters, e.g., stage and grade. In addition, aberrant p53 status was significantly associated with shorter disease-free survival (P < 0.0001) and poor response to therapy (P < 0.0001). In the most common subgroups, stage III and stage I carcinomas, 5-year overall survival rates for patients showing normal p53 vs. aberrant p53 were 72% vs. 19% (P < 0.0001) and 99% vs. 56% (P < 0.0001), respectively. CONCLUSION: P53 expression status divides serous ovarian carcinomas into two distinct subtypes: one with a relatively good prognosis and the other with a particularly poor outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Tenascin-C expression correlates with prognosis in gastric cancer.

OBJECTIVES: Tenascin-C is a hexameric extracellular matrix glycoprotein that is expressed during embryonic development and re-expressed in proliferative processes such as wound healing and tumorigenesis. Stromal tenascin-C may block tumor invasion and thus have a significant influence on tumor spread and prognosis. METHODS: In the present study, tissue expression of stromal tenascin-C was studied by immunohistochemistry in a series of 314 patients with gastric cancer. RESULTS: Strong tenascin-C positivity was seen in the stroma of the tumor in 122 (39%) cases. There was a correlation between strong tenascin-C expression and low stage (p = 0.002), superficial tumor penetration (p = 0.02), location of tumor at the distal third of the stomach (p = 0.03), and potentially curative surgery (p = 0.008). No significant correlation was found between tenascin-C positivity and nodal status, distant metastases, age, Laurén classification, gender, tumor size, or Borrmann classification. The cumulative 5-year survival in patients with strong tenascin-C expression was 42% compared to 26% in those with negative-to-moderate expression (p = 0.0053). In multivariate survival analysis stratified for estimated cure of surgery, stage of disease was the only independent prognostic factor. CONCLUSION: In conclusion, tenascin-C expression seems to correlate with cancer related survival in patients with gastric cancer, but may not add significant prognostic information to that provided by TNM stage.

Aged↗