Dataset Information

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

ABSTRACT: Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

SUBMITTER: Linders D

PROVIDER: S-EPMC8002064 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

Linders Daan D Deken Marion M van der Valk Maxime M Tummers Willemieke W Bhairosingh Shadhvi S Schaap Dennis D van Lijnschoten Gesina G Zonoobi Elham E Kuppen Peter P van de Velde Cornelis C Vahrmeijer Alexander A Farina Sarasqueta Arantza A Sier Cornelis C Hilling Denise D

Diagnostics (Basel, Switzerland) 20210314 3

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasmino ...[more]

PMID: 33799475

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Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.

Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific “signature” associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (χ2=11•793; p= 0•001) and TS expression (χ2=10•589; p= 0•001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer.

Project description:BackgroundPatients with locally advanced rectal cancer (LARC) have an improved prognosis if achieved a pathological complete response (pCR) on account of neoadjuvant chemoradiation therapy (nCRT). However, the proportion of patients achieving pCR is only 8-24%. The purpose of this study was to explore whether the addition of consolidation chemotherapy to nCRT could improve pCR rate in patients with LARC.Materials and methodsThe subjects were 144 individuals with clinical stage II (T3-4, N0) or III (any T, N1-2) LARC who had received neoadjuvant CRT followed by total mesorectal excision (TME). Eighty-three patients in the consolidation chemotherapy group received two cycles XELOX between CRT and TME, while 61 patients in the standard treatment group without consolidation chemotherapy. The pCR (ypT0N0), tumor downstaging (ypT0-2N0) after TME and adverse events (AEs) during and post treatment were compared between the treatment groups using multivariable logistic regression analysis. To adjust the unbalanced variables for the primary endpoint, logistic regression analysis and stratified analysis were performed.ResultsThe consolidation chemotherapy group improved pCR rate (19.3% vs 4.9%, p = 0.01) and tumor downstaging rate (45.8% vs 24.6%, p = 0.009) compared to the standard treatment group. After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, patients with consolidation chemotherapy were more likely to reach pCR (adjusted odds ratio 4.91, 95% CI [1.01-23.79], p = 0.048). AEs during and post treatment in the two groups were 54.1% vs 49.3% (p = 0.57), respectively. In addition, the incidence of any grade 1-2 AEs in the two groups was 93.4% vs 95.1% (p = 0.93), while the incidence of grade 3 AEs was 1.6% versus 2.4% (p = 0.74), respectively. No grade 4 AEs occurred in two groups.ConclusionsThe addition of neoadjuvant consolidation chemotherapy after CRT significantly increased the pCR rate and did not increase the AEs during and post treatment and in patients with LARC.

Dataset Information

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

Publications

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

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