scholarly journals Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ihsane El Otmani ◽  
Fatima El Agy ◽  
Sanae El Baradai ◽  
Laila Bouguenouch ◽  
Nada Lahmidani ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Distant Metastasis ◽  
Therapeutic Response ◽  
High Expression ◽  
Prognostic Impact ◽  
P53 Expression ◽  
Incomplete Response ◽  
Pathologic Features ◽  
Her 2

Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen’s data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p=0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p=0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p=0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p=0.016, r=0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.

scholarly journals Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1689 ◽  
Author(s):  
Bianca Grosser ◽  
Meike Kohlruss ◽  
Julia Slotta-Huspenina ◽  
Moritz Jesinghaus ◽  
Nicole Pfarr ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Surgical Resection ◽  
Molecular Subtypes ◽  
Strong Association ◽  
Multivariable Analysis ◽  
Tumor Localization ◽  
Prognostic Impact ◽  
P53 Expression ◽  
Prognostic Effect ◽  
Barr Virus

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.

scholarly journals The risk factors of local recurrence and distant metastasis on pT1/T2N0 mid-low rectal cancer after total mesorectal excision

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
I-Li Lai ◽  
Jeng-Fu You ◽  
Yih-Jong Chern ◽  
Wen-Sy Tsai ◽  
Jy-Ming Chiang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
Local Recurrence ◽  
Distant Metastasis ◽  
Resection Margin ◽  
Radical Resection ◽  
Hazard Ratio ◽  
Low Rectal Cancer ◽  
Distal Resection Margin ◽  
Lymph Node Yield

Abstract Background Radical resection is associated with good prognosis among patients with cT1/T2Nx rectal cancer. However, still some of the patients experienced cancer recurrence following radical resection. This study tried to identify the postoperative risk factors of local recurrence and distant metastasis separately. Methods This retrospective, single-center study comprised of 279 consecutive patients from Linkou branch of Chang Gung Memorial Hospital in 2005–2016 with rectal adenocarcinoma, pT1/T2N0M0 at distance from anal verge ≤ 8cm, who received curative radical resection. Results The study included 279 patients with pT1/pT2N0 mid-low rectal cancer with median follow-up of 73.5 months. Nineteen (6.8%) patients had disease recurrence in total. Nine (3.2%) of them had local recurrence, and fourteen (5.0%) of them had distant metastasis. Distal resection margin < 0.9 (cm) (hazard ratio = 4.9, p = 0.050) was the risk factor of local recurrence. Preoperative carcinoembryonic antigen (CEA) ≥ 5 ng/mL (hazard ratio = 9.3, p = 0.0003), lymph node yield (LNY) < 14 (hazard ratio = 5.0, p = 0.006), and distal resection margin < 1.4cm (hazard ratio = 4.0, p = 0.035) were the risk factors of distant metastasis. Conclusion For patients with pT1/pT2N0 mid-low rectal cancer, current multidisciplinary treatment brings acceptable survival outcome. Insufficient distal resection margin attracted the awareness of risk factors for local recurrence and distant metastasis as a foundation for future research.

scholarly journals High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

2021 ◽  
Vol 28 (4) ◽  
pp. 2373-2384
Author(s):  
Tzu-Ju Chen ◽  
Yu-Feng Tian ◽  
Chia-Lin Chou ◽  
Ti-Chun Chan ◽  
Hong-Lin He ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Concurrent Chemoradiotherapy ◽  
Therapeutic Response ◽  
Tumor Regression ◽  
Free Survival ◽  
Cancer Transcriptome ◽  
Poor Outcomes ◽  
Univariate Analyses ◽  
Local Recurrence Free Survival

Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p < 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p < 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p < 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.

1034 Preoperative radiotherapy for resectable rectal cancer: Improved local control is prognostic for distant metastasis occurrence and survival

1996 ◽  
Vol 36 (1) ◽  
pp. 261 ◽  
Author(s):  
Robert A. Zlotecki ◽  
William M. Mendenhall ◽  
Edward M. Copeland ◽  
Jean-Nicholas Vauthey ◽  
Robert D. Marsh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Control ◽  
Distant Metastasis ◽  
Preoperative Radiotherapy ◽  
Resectable Rectal Cancer

Surgical resection following reirradiation for recurrent rectal cancer

1994 ◽  
Vol 30 ◽  
pp. 277
Author(s):  
Vasudha Lingareddy ◽  
Jan Rakinic ◽  
Gerald Marks ◽  
Mohammed Mohiuddin
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Recurrent Rectal Cancer

Outcome of right- and left-sided colonic and rectal cancer following surgical resection

2010 ◽  
Vol 13 (8) ◽  
pp. 884-889 ◽  
Author(s):  
S. A. Suttie ◽  
I. Shaikh ◽  
R Mullen ◽  
A. I. Amin ◽  
T. Daniel ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection

Neorectal Irritability After Short-Term Preoperative Radiotherapy and Surgical Resection for Rectal Cancer

2008 ◽  
Vol 104 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Roel Bakx ◽  
Annemiek Doeksen ◽  
J Frederik M Slors ◽  
Willem A Bemelman ◽  
J Jan B van Lanschot ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Preoperative Radiotherapy ◽  
Short Term

scholarly journals HER-2 Expression in Immunohistochemistry Has No Prognostic Significance in Gastric Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Test Score ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Curative Surgery ◽  
Regional Lymph Nodes ◽  
Poorly Differentiated ◽  
Her 2 ◽  
Gastric Cancer Patients

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P=0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient’s age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.

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