MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease

Oncology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Athanasios Tampakis ◽  
Ekaterini Christina Tampaki ◽  
Afroditi Nonni ◽  
Michael Kontos ◽  
Gerasimos Tsourouflis ◽  
...  

<b><i>Background:</i></b> Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. <b><i>Patients and Methods:</i></b> Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. <b><i>Results:</i></b> MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (<i>p</i> &#x3c; 0.001), higher T classification (<i>p</i> = 0.007), the presence of lymph node metastasis (<i>p</i> &#x3c; 0.001), vascular (<i>p</i> = 0.013) and perineural invasion (<i>p</i> = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, <i>p</i> &#x3c; 0.001) and 5-year overall survival (40.8 vs. 91%, <i>p</i> &#x3c; 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056–0.329, <i>p</i> &#x3c; 0.001) and overall survival (HR 0.144 [95% CI) = 0.049–0.419, <i>p</i> &#x3c; 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. <b><i>Conclusions:</i></b> High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5049-5049
Author(s):  
Guilherme Fleury Perini ◽  
Egyla M Cavalcante ◽  
Joao Garibaldi Rezende ◽  
Davimar Miranda Borducchi ◽  
Fernanda Cunha Vieira ◽  
...  

Abstract Introduction In 1998, Hasenclever et al published the International Prognostic Factor for patients with advanced stage classical Hodgkin lymphoma (cHL). Since then, the IPS has been considered the most important prognostic score for cHL and has been validated in different populations, and also in early stage cHL. From the seven factors analyzed in the IPS, albumin is the only that can be influenced by environmental, economic and nutritional status. We hypothesized if, in developing countries, albumin should still be a prognostic factor, and if so, what is the ideal cutoff value. Objectives To assess if albumin at diagnosis of cHL patients in Brazil was prognostic for overall survival (OS) and progression free survival (PFS) and what would be the best cutoff. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1996 To January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 179 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 125 (68.9%) of all patients. Median age at diagnosis was 28 years old (ranging from 13-76). Only 22.9% of patients presented with early stage disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients. Consolidation radiotherapy was done in 48.6%. Median serum albumin was 3.74 (range: 1.34 – 5.52). Median albumin for patients treated in private hospital was 3.6 (range: 2.7 – 4.7) in contrast to patients treated in public hospitals with a median level of 3.0 (range: 1.34 – 5.52), although this difference was not statistically different. Overall responses were: CR in 90%, Partial response/Refractory disease in 10%; one patient died due to treatment-related toxicity. Overall Survival (OS) for the entire group was 93% in 5 years (CI95% 87-96%), with a progression free survival (PFS) of 79% (CI95% 73-86%). When applying the cutoff of 4g/dL, albumin was not related to OS (91% vs 98%, p=ns) or PFS (85 vs 77%, p=ns). However, an albumin value greater than 2g/dL was related to a better OS (94% vs 71%, p=0.01). Conclusions Prognostic factors may differ from different studied populations. This is particularly truth for albumin, which is the only IPS factor influenced by the environment. In our study, however, albumin was not significantly related to OS or PFS, unless when a cutoff of 2g/dL was used. Disclosures: No relevant conflicts of interest to declare.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5516-5516
Author(s):  
L. A. Cantrell ◽  
L. Havrilesky ◽  
D. O'Malley ◽  
M. Liotta ◽  
A. A. Secord ◽  
...  

5516 Background: The treatment of early stage uterine carcinosarcoma is controversial. We sought to retrospectively review factors that influence progression and survival. Methods: A retrospective, multi-institution study of women diagnosed from 1997–2007 was performed. Postoperative treatment included either observation (OBS), RT (brachytherapy, whole pelvic, or combination), chemotherapy (CT) alone or with RT (CT+RT). Data collected included time to recurrence, overall survival, and sites of recurrence. Statistics included ANOVA and Kaplan Meier. Results: One hundred and forty-six patients were diagnosed with early stage (stages 1 and 2) uterine carcinocarcoma. The median age at diagnosis was 68 years (range:40–91). The majority (62%) were Caucasian, 49 (34%) were African-American and the remainder were other ethnicities. One hundred and seventeen had stage 1 disease and 29 had stage 2. The majority of patients (N = 54, 37 %) were observed, 36 (25%) were treated with CT, 31 (21%) were treated with RT and 17 (12%) were treated with CT + RT. The median progression free survival (PFS) for patients diagnosed with early stage disease was 16.7 months for the OBS cohort and 38.2 months for the CT cohort (p < 0.01). Median overall survival was 23 months for the OBS cohort and 39.3 months for the CT cohort (p = 0.02). The cohorts that underwent RT or CT+RT had improved median progression free (29.9, 20 months) and overall survival (31.7, 20.8 months) as compared to the OBS cohort, however this was not a statistically significant difference. Conclusions: We report on the largest experience in the literature on early stage uterine carcinosarcoma and the first to show that women with early stage disease may benefit from adjuvant chemotherapy. The role of radiation therapy or combination chemotherapy and radiation could not be adequately assessed from this retrospective analysis, but a trend toward improved survival was present. Prospective trials evaluating the best treatment for patients with early stage carcinosarcoma of the uterus should be undertaken to better answer this question. No significant financial relationships to disclose.


Medicina ◽  
2009 ◽  
Vol 45 (8) ◽  
pp. 615 ◽  
Author(s):  
Eduardas Aleknavičius ◽  
Konstantinas Valuckas ◽  
Birutė Aleknavičienė ◽  
Laura Norkienė ◽  
Giedrė Smailytė

During last decades, there are strengthening attitudes to optimize the treatment of Hodgkin’s lymphoma considering prognostic groups and risk factors. Based on the data of Vilnius University Clinics, a retrospective study was carried out, and treatment methods and outcomes of the patients treated during 1999– 2004 were analyzed. Medical histories of 114 patients younger than 60 years were reviewed. Median age was 28 years. In 83% of cases, classic nodular sclerotic Hodgkin’s lymphoma was diagnosed. Advanced-, intermediate-, and early-stage disease was diagnosed in 55%, 38%, and 7% of cases, respectively. The patients with early-stage disease underwent four ABVD chemotherapy courses; 88% of them underwent radiotherapy afterwards. The patients with intermediate-stage disease underwent 4–6 courses of ABVD or in minor cases (12% of patients with intermediate-stage disease) – 4 standard BEACOPP chemotherapy courses. After this treatment, 88% of patients with intermediate-stage disease underwent radiotherapy. Patients with advanced-stage disease underwent 8 escalate (44%) or standard BEACOPP (29%) chemotherapy courses. More than half of these patients (71%) underwent radiotherapy after chemotherapy. Patient follow-up median was 65 months. One hundred seven patients (94%) after primary treatment achieved complete remission, in 7 patients (6%) primary progression was observed, 12 patients (11%) relapsed, and 8 patients died. Overall survival and event-free survival in patients with early-stage disease was 100%. Overall survival in patients with early/intermediate- and advanced-stage disease was 95.1% and 84.0%, respectively. Event-free survival in patients with early/intermediate- and advanced-stage disease was 91.7% and 76.2%, respectively. In the groups of intermediate- and advanced-stage disease, the results of treatment were worse in the subgroup, which underwent extended-field radiotherapy (P<0.05). Overall survival in the group of patients with advanced-stage disease was the best who underwent ABVD scheme, but the event-free survival (70.6%) and disease-free survival (81.3%) in ABVD subgroup were worse compared to BEACOPP subgroup. According to our results, there was no statistically significant difference in survival of patients with advanced-stage disease who underwent or did not radiotherapy (P>0.05).


2006 ◽  
Vol 24 (12) ◽  
pp. 1892-1897 ◽  
Author(s):  
Jeffrey A. Meyerhardt ◽  
Andrew X. Zhu ◽  
Peter C. Enzinger ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
...  

Purpose To investigate the combination of erlotinib, capecitabine, and oxaliplatin in patients who were previously treated for metastatic colorectal cancer. Patients and Methods Patients were eligible if they had metastatic colorectal cancer that progressed, were intolerant to first-line chemotherapy, or had disease recurrence within 1 year of adjuvant therapy for early-stage disease. Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine at 1,000 mg/m2 (reduced to 750 mg/m2 after the first 13 patients) twice a day on days 1 to 14, and intravenous oxaliplatin at 130 mg/m2 on day 1. Results Thirty-two patients were enrolled onto this phase II study. By intention-to-treat analyses, eight patients (25%) experienced a partial response and 14 patients (44%) had stable disease for at least 12 weeks. The median progression-free survival was 5.4 months and the median overall survival was 14.7 months. These results were essentially unchanged when limited to the cohort of patients (78%) who received prior irinotecan for metastatic colorectal cancer. Most common grade 3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%), dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced with a lower starting dose of capecitabine. Conclusion The combination of capecitabine, oxaliplatin, and erlotinib seems to have promising activity against metastatic colorectal cancer in patients who received prior chemotherapy, with a relatively higher response rate and progression-free survival compared with previous reports of either infusional FU, leucovorin, and oxaliplatin or capecitabine and oxaliplatin in similar patient populations.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.


2022 ◽  
Vol 12 ◽  
Author(s):  
Yujiao Deng ◽  
Yuxiu Xie ◽  
Meng Wang ◽  
Peng Xu ◽  
Bajin Wei ◽  
...  

Background: Antihypertensive drugs might play a key role in the risk and poor prognosis of colorectal cancer. However, current epidemiologic evidence remains inconsistent. The aim of this study is to quantify the association between antihypertensive drugs and colorectal cancer.Methods: To identify available studies, we systematically searched electronic databases: PubMed, Web of Science, Embase, Cochrane Library. The risk estimates and their corresponding 95% confidence intervals (CIs) were collected and analyzed by using random-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: Overall, 37 observational studies were included in this analysis (26 studies with cohort design, three studies with nested case-control design, and 8 studies with case-control design). Antihypertensive drugs did not present a significant effect on the risk or overall survival of patients with colorectal cancer [Risk ratio (RR) = 1.00, 95% CI: 0.95–1.04; Hazard ratio (HR) = 0.93, 95% CI: 0.84–1.02]. In the subgroup analysis, diuretics use was significantly associated with a worse overall survival of patients with colorectal cancer (HR = 1.27; 95% CI: 1.14–1.40). However, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was associated with improved progression-free survival of patients who suffered from colorectal cancer (HR = 0.83; 95% CI: 0.72–0.95).Conclusion: Antihypertensive drug usage did not influence the risk and overall survival of patients with colorectal cancer in general. Further investigation reminded us that diuretics use might reduce the overall survival time in colorectal cancer patients, whereas those who took Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers had a longer progression-free survival.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1013
Author(s):  
Chara Papadaki ◽  
Stavroula Manolakou ◽  
Eleni Lagoudaki ◽  
Spyros Pontikakis ◽  
Despo Ierodiakonou ◽  
...  

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.


2012 ◽  
Vol 27 (3) ◽  
pp. 212-218 ◽  
Author(s):  
Hong-Qiang Guo ◽  
Guo-Liang Huang ◽  
Ou-Fei Liu ◽  
Yan-Yan Liu ◽  
Zhi-Hua Yao ◽  
...  

p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.


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