Impact of CDKN2A/b status in pancreatic cancer (PC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 759-759
Author(s):  
Kaitlin Annunzio ◽  
Claire Griffiths ◽  
Igli Arapi ◽  
Matthew Lasowski ◽  
Arun K. Singavi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Marginal Effect ◽  
Prognostic Impact ◽  
Borderline Resectable ◽  
Curative Intent ◽  
Cox Regression Analysis ◽  
Response To Chemotherapy

759 Background: PC is a lethal disease with limited treatment options. We utilized Comprehensive Genomic Profiling (CGP) to identify putative prognostic and/or predictive biomarkers. Methods: We retrospectively reviewed PC patients (pts) at our institution who underwent CGP utilizing the Foundation One assay. CGP was performed on hybrid-capture, adaptor ligation-based libraries for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. PC pts were categorized by clinical stage – localized (resectable and borderline resectable PC; LPC), locally advanced (LAPC) and metastatic (mPC). Effect of gene alterations (GAs) with at least 10% prevalence were analyzed. The marginal effect of each gene on radiographic response and survival outcomes was estimated using proportional odds and multivariate Cox regression analysis, respectively, adjusting for stage. Results: Ninety-three pts were identified - median age was 63, 55% were male, and 50% were smokers. Clinical stage at diagnosis was LPC, LAPC and mPC in 42 (45%), 23 (25%) and 28 (30%) pts, respectively. The most commonly altered genes were KRAS (94%), TP53 (75%), CDKN2A (41.2%) and SMAD4 (32.9%). All patients were microsatellite stable and the median tumor mutational burden was 1.7. 5-FU (52%) or Gemcitabine (46%) based chemotherapy combinations were utilized as the first systemic therapy. Median overall survival for patients with LPC, LAPC and mPC were 30.7, 28.8 and 9.6 months respectively. Thirty-eight (91%) pts with LPC underwent curative intent surgery compared to 15 (65%) pts with LAPC (p = 0.019). Thirty-five (95%) pts with wild type (WT) CDKN2A and 47 (94%) pts with WT CDKN2B underwent curative intent surgery compared to 13 (65%) and 1(14%) pt(s) with GAs in CDKN2A and CDKN2B respectively (p = 0.003 and p < 0.0001 respectively). The response to chemotherapy was statistically significantly higher in pts with WT CDKN2A (53%) and CDKN2B (48%) compared to pts with GAs in CDKN2A (19%) and CDKN2B (12%) (p = 0.03 and p = 0.05, respectively). Conclusions: GAs in CDKN2A/B may have a predictive and possibly a prognostic impact. The clinical validity and biological relevance of these findings need to be further explored in larger studies.

scholarly journals Changes and Prognostic Impact of Inflammatory Nutritional Factors During Neoadjuvant Chemoradiotherapy for Patients with Resectable and Borderline Resectable Pancreatic Cancer

2020 ◽  
Author(s):  
Minoru Oshima ◽  
Keiichi Okano ◽  
Hironobu Suto ◽  
Yasuhisa Ando ◽  
Hideki Kamada ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Score ◽  
Neoadjuvant Chemoradiotherapy ◽  
Glasgow Prognostic Score ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Borderline Resectable ◽  
Nutritional Factors ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio

Abstract BackgroundInflammatory nutritional factors, such as the neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), and C-reactive protein/albumin (CRP/Alb) ratio, have prognostic values in many types of cancer. In this study, the prognostic values of inflammatory nutritional scores were evaluated in the patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemoradiotherapy (NACRT).MethodsA total of 49 patients who underwent pancreatectomy after NACRT from September 2009 to May 2016 were enrolled. The NACRT consisted of hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) delivered 5 days/week for 2 weeks before pancreatectomy. Inflammatory nutritional scores were determined before and after NACRT in this series. ResultsThe median NLR increased after NACRT (from 2.067 to 3.302), with statistical difference (p<0.001). In multivariate Cox regression analysis, high pre-NACRT mGPS (2 or 1; p=0.0478) and significant increase in CRP/Alb ratio after NACRT (≧0.077; p=0.0036) were associated with shorter overall survival. All patients were divided into two groups according to the ΔCRP/Alb ratio after NACRT: the group with high ΔCRP/Alb ratio (≧0.077) and the group with low ΔCRP/Alb ratio (<0.077). The group with high ΔCRP/Alb ratio after NACRT (n=13) not only had higher post-NACRT CRP levels (p<0.001) but also had lower post-NACRT Alb levels (p=0.002). Patients in the group with high ΔCRP/Alb ratio lost more body weight during NACRT (p=0.03).ConclusionIn addition to pre-NACRT mGPS, ΔCRP/Alb after NACRT could provide prognostic value in the patients with PDAC treated by NACRT.

Effect of nutritional status and support on survival in esophageal cancer patients undergoing combined modality therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20641-e20641
Author(s):  
J. P. Plastaras ◽  
J. C. Haynes ◽  
R. Mick ◽  
L. M. Hertan ◽  
A. I. Urdaneta ◽  
...  
Keyword(s):  
Weight Loss ◽  
Esophageal Cancer ◽  
Nutritional Status ◽  
Cox Regression ◽  
Combined Modality Therapy ◽  
Locally Advanced ◽  
Nutritional Supplements ◽  
Curative Intent ◽  
Cox Regression Analysis ◽  
The Impact

e20641 Background: Baseline nutritional status is associated with clinical outcomes in esophageal cancer. Moreover, nutritional support during chemoradiation has been shown to improve outcomes in other disease sites. This retrospective study evaluated the impact of nutritional interventions and baseline nutritional status on outcomes in patients (pts) with locally advanced esophageal cancer. Methods: A retrospective review was performed of 132 pts treated with curative intent using radiation (RT) between 1986 and 2007 at the Hospital of the University of Pennsylvania. The median age of the population was 60 years (range: 33–86). Esophagectomy was performed in 70%, with adjuvant RT in 60% and neoadjuvant RT in 40%. Concurrent chemotherapy was given to 85% of the group. Nutritional counseling was provided to 83% of pts. During RT, oral or enteral nutritional supplements were provided to 77% of pts and intravenous fluids (IVF) were given to 38%. Median follow-up was 14.1 months. Results: Median survival from end of radiation was 1.5 yrs. Median absolute and percentage weight loss during RT were 6.2 lbs and 3.8%, respectively. Median percentage decrease in hemoglobin and albumin were 5.7% and 9.1%, respectively. Univariable Cox regression analysis demonstrated a statistically significant association between weight loss of ≥5 lbs during RT and worse survival (HR 1.74, 95% CI 1.09 - 2.79, p=0.02). Decrease in hemoglobin of 5% or more (HR 1.22, 95% CI 0.59 - 2.54) and decrease in albumin of 10% or more (HR 1.09, 95% CI 0.48 - 2.48) were not associated with survival. Patients who received only nutritional supplements during RT survived significantly longer (p=0.03) than pts who received IVF regardless of nutritional supplementation (HR 2.12, 95% CI 1.12 - 4.01) or pts who received neither nutritional supplements nor IVF (HR 1.8, 95% CI 1.03 - 3.14). Conclusions: Weight loss during RT predicted for worse survival. Nutritional factors before and during RT may be important in outcomes in patients with esophageal cancer and may be modifiable. The use of IVF may be a potential indicator of worse prognosis. Future prospective studies should consider these factors in trial design. No significant financial relationships to disclose.

Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer

2009 ◽  
Vol 27 (10) ◽  
pp. 1549-1556 ◽  
Author(s):  
Dorothea Weckermann ◽  
Bernhard Polzer ◽  
Thomas Ragg ◽  
Andreas Blana ◽  
Günter Schlimok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Cox Regression ◽  
Systemic Disease ◽  
Disseminated Tumor Cells ◽  
Comparative Genomic ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
Cox Regression Analysis

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

2014 ◽  
Vol 32 (27) ◽  
pp. 2983-2990 ◽  
Author(s):  
Andrew R. Davies ◽  
James A. Gossage ◽  
Janine Zylstra ◽  
Fredrik Mattsson ◽  
Jesper Lagergren ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Esophagogastric Junction ◽  
Cox Regression ◽  
Tumor Regression ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Response To Treatment ◽  
Cox Regression Analysis ◽  
Systemic Recurrence

Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. Conclusion The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Complete Response ◽  
Cox Regression Analysis

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

Toll-like receptor 3 is a potential prognosis marker and associated with immune infiltration in stomach adenocarcinoma

2021 ◽  
pp. 1-17
Author(s):  
Zhihao Huang ◽  
Aoxiao He ◽  
Jiakun Wang ◽  
Hongcheng Lu ◽  
Xiaoyun Xu ◽  
...  
Keyword(s):  
Cox Regression ◽  
Clinical Stage ◽  
Mrna Level ◽  
Positive Association ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
Qrt Pcr ◽  
Tlr3 Expression ◽  
Immune Biomarkers ◽  
Prognosis Marker

BACKGROUND: Toll-like receptors participate in various biological mechanisms, mainly including the immune response and inflammatory response. Nevertheless, the role of TLRs in STAD remains unclear. OBJECTIVE: We aimed to explore the expression, prognosis performance of TLRs in STAD and their relationship with immune infiltration. METHODS: Student’s t-test was used to evaluate the expression of TLRs between STAD tissues and normal tissues. Kaplan-Meier method was applied to explored the prognosis value of TLRs in STAD. And qRT-PCR validated their expression and prognosis value. Spearman’s correlation analysis and Wilcoxon rank-sum test were used to assess the association between TLRs and immune infiltration in STAD. RESULTS: The mRNA level of TLR3 was downregulated in STAD. We summarized genetic mutations and CNV alteration of TLRs in STAD cohort. Prognosis analysis revealed that STAD patients with high TLR3 expression showed better prognosis in OS, FP and PPS. The result of qRT-PCR suggested that TLR3 expression was decreased in STAD tissues and STAD patients with high TLR3 mRNA level had a better OS. Univariate and multivariate cox regression analysis suggested TLR3 expression and clinical stage as independent factors affecting STAD patients’ prognosis. A positive association existed between TLR3 expression and the abundance of immune cells and the expression of various immune biomarkers. Furthermore, key targets related to TLR3 were identified in STAD, mainly including MIR-129 (GCAAAAA), PLK1, and V$IRF1_01. CONCLUSIONS: Our result demonstrated TLR3 as a prognosis marker and associated with immune infiltration in STAD.

scholarly journals Complex segmentectomy in the treatment of stage IA non-small-cell lung cancer

2019 ◽  
Vol 57 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Yoshinori Handa ◽  
Yasuhiro Tsutani ◽  
Takahiro Mimae ◽  
Yoshihiro Miyata ◽  
Morihito Okada
Keyword(s):  
Lung Cancer ◽  
Regression Analysis ◽  
Cancer Treatment ◽  
Cox Regression ◽  
Clinical Stage ◽  
Cancer Control ◽  
Cox Regression Analysis ◽  
Lung Cancer Treatment ◽  
Clinical Stage Ia ◽  
Stage Ia

AbstractOBJECTIVESAlthough segmentectomy for lung cancer has been widely accepted, complex segmentectomy, which creates several, intricate intersegmental planes, remains controversial. Potential arguments include risk of incurability and ‘failure of cancer control’. We compared the outcomes of complex segmentectomy versus lobectomy and evaluated its use in lung cancer treatment.METHODSWe retrospectively reviewed clinical stage IA lung cancer patients who underwent complex segmentectomy (n = 99) or location-adjusted lobectomy (n = 94) between April 2009 and December 2017. Clinicopathological and postoperative results were compared. Factors affecting survival were assessed by the Kaplan–Meier method and the Cox regression analysis.RESULTSNo significant differences were detected in 30-day mortality (0% vs 0%), overall complications (26.3% vs 21.3%) and prolonged air leakage (11.1% vs 9.6%) rates between the 2 groups, respectively. Comparable results were obtained for 5-year overall (93.5% vs 96.4%, respectively; P = 0.21) or recurrence-free (92.3% vs 88.5%, respectively; P = 0.82) survivals after complex segmentectomy or lobectomy. There were 2 (2.0%) recurrences after complex segmentectomy and 7 (7.5%) after lobectomy (P = 0.094), with 0 (0%) margin relapses in each group. Multivariable Cox regression analysis revealed that complex segmentectomy and lobectomy had a numerically similar impact on recurrence-free survival (hazard ratio 0.93, 95% confidence interval 0.32–2.69; P = 0.90).CONCLUSIONSComplex segmentectomy can provide acceptable short- and long-term outcomes in lung cancer treatment.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

scholarly journals LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Longzhen Piao ◽  
Zhaoting Yang ◽  
Ying Feng ◽  
Chengye Zhang ◽  
Chunai Cui ◽  
...  
Keyword(s):  
Cox Regression ◽  
Transmembrane Protein ◽  
Small Cell Lung Carcinoma ◽  
Clinical Stage ◽  
Small Cell ◽  
Cancer Prognosis ◽  
Normal Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis ◽  
Potential Biomarker

Abstract Background Although the leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is one of the mitochondrial inner membrane proteins that is involved in cancer prognosis in various tumors, LETM1 as a biomarker for prognostic evaluation of non-small cell lung carcinoma (NSCLC) has not been well studied. Methods To address this issue, we used 75 cases NSCLC, 20 cases adjacent normal lung tissues and NSCLC cell lines. We performed immunohistochemistry staining and western blot analysis as well as immunofluorescence imaging. Results Our studies show that expression of LETM1 is significantly correlated with the lymph node metastasis (p = 0.003) and the clinical stage (p = 0.005) of NSCLC. The Kaplan-Meier survival analysis revealed that NSCLC patients with positive expression of LETM1 exhibits a shorter overall survival (OS) rate (p = 0.005). The univariate and multivariate Cox regression analysis indicated that LETM1 is a independent poor prognostic marker of NSCLC. In addition, the LETM1 expression is correlated with cancer stemness-related gene LGR5 (p < 0.001) and HIF1α expression (p < 0.001), but not with others. Moreover, LETM1 expression was associated with the expression of cyclin D1 (p = 0.003), p27 (p = 0.001), pPI3K(p85) (p = 0.025), and pAkt-Thr308 (p = 0.004). Further, our studies show in LETM1-positive NSCLC tissues the microvessel density was significantly higher than in the negative ones (p = 0.024). Conclusion These results indicate that LETM1 is a potential prognostic biomarker of NSCLC.

Prognostic Significance of Angiogenesis and Ki-67, p53, and p21 Expression: A Population-Based Endometrial Carcinoma Study

1999 ◽  
Vol 17 (5) ◽  
pp. 1382-1382 ◽  
Author(s):  
Helga B. Salvesen ◽  
Ole Erik Iversen ◽  
Lars A. Akslen
Keyword(s):  
High Risk ◽  
Endometrial Carcinoma ◽  
Cox Regression ◽  
Figo Stage ◽  
Population Based ◽  
Prognostic Impact ◽  
Histologic Type ◽  
Ki 67 ◽  
Cox Regression Analysis

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P ≤ .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P ≤ .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.

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