Prognostic Impact of Histologic Type in Curatively Resected Stage IV Colorectal Cancer: A Japanese Multicenter Retrospective Study

Shibata, Junichi; Kawai, Kazushige; Nishikawa, Takeshi; Tanaka, Toshiaki; Tanaka, Junichiro; Kiyomatsu, Tomomichi; Hata, Keisuke; Nozawa, Hiroaki; Kazama, Shinsuke; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Sugihara, Kenichi; Watanabe, Toshiaki

doi:10.1245/s10434-015-4846-z

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…Although a significantly worse prognosis for poorlydifferentiated adenocarcinoma was observed here, similar to previous reports (20,21,43), genomic analyses of somatic mutations or MSI were not carried out in the SOFT trial. Information on tumor location (right or left side) was also not recorded in this trial, other than whether the tumor was in the colon or rectum.…”

Section: Discussionsupporting

confidence: 86%

“…Several reports have documented a poor prognosis for advanced resectable colorectal cancer with poorlydifferentiated adenocarcinoma histology relative to wellor moderately-differentiated adenocarcinoma. However, whether this also applies to unresectable metastatic cancer during palliative chemotherapy was not known (20,21). Poorly-differentiated adenocarcinoma is closely associated with the presence of microsatellite instability (MSI) and is found more often in females.…”

Section: Impact Of Sex and Histology On The Therapeutic Effects Of Fluoropyrimidines And Oxaliplatin Plus Bevacizumab For Patients With Mmentioning

confidence: 99%

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Impact of sex and histology on the therapeutic effects of fluoropyrimidines and oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in the SOFT trial

Yamada

Muro

Takahashi

et al. 2020

GHM

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Mechanisms accounting for sex differences in the incidence of adverse events caused by fluoropyrimidine treatments, and histologic differences in efficacy are insufficiently understood. We determined differences between the sexes in terms of the safety of S-1 plus oxaliplatin (SOX)/bevacizumab-versus-l-leucovorin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX)/bevacizumab, and the impact of histology on their therapeutic effects, in 512 unresectable metastatic colorectal cancer patients from the SOFT phase III study. Nausea (OR: 2.88, P < 0.001) and vomiting (OR: 3.04, P = 0.005) occurred more frequently in females than males treated with SOX/bevacizumab, while nausea (OR: 2.12, P = 0.006), vomiting (OR: 3.26, P = 0.004), leukopenia (OR: 2.61, P < 0.001), neutropenia (OR: 2.92, P < 0.001), and alopecia (OR: 4.13, P < 0.001) were higher in females on FOLFOX/bevacizumab. Mean relative dose intensities (RDIs) of S-1 during all cycles of SOX/bevacizumab were significantly lower in females (73.9%) than males (81.5%) (P < 0.001), while RDIs of continuous infusion of 5-FU in the FOLFOX/bevacizumab regimen were 75.0% in females and 80.5% in males (P = 0.005). No significant differences in efficacy with regard to overall survival (OS) and progressionfree survival (PFS) were identified between the sexes for either SOX/bevacizumab or FOLFOX/bevacizumab treatment. Patients with poorly-differentiated adenocarcinoma had significantly worse OS (HR: 2.72, 95% CI: 1.67-4.44, P < 0.0001) and PFS (HR: 1.89, 95% CI: 1.18-3.02, P = 0.0079) than patients with well-or moderately-differentiated adenocarcinoma. Female patients experienced more frequent and severe adverse reactions to SOX/bevacizumab and FOLFOX/bevacizumab and a worse prognosis for poorly-differentiated adenocarcinoma were confirmed in this phase III study. This warrants further translational research to identify the responsible mechanisms.

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Section: Discussionsupporting

confidence: 86%

Section: Impact Of Sex and Histology On The Therapeutic Effects Of Fluoropyrimidines And Oxaliplatin Plus Bevacizumab For Patients With Mmentioning

confidence: 99%

Impact of sex and histology on the therapeutic effects of fluoropyrimidines and oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in the SOFT trial

Yamada

Muro

Takahashi

et al. 2020

GHM

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“…Most existing studies evaluating the pathological impact have primarily focused on CRC [2,7,[17][18][19][20][21] rather than on mCRC. Only a few articles have mentioned the prognostic implications of MUC in resected mCRC [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare surgical value

Jiang

et al. 2016

Journal of Surgical Oncology

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“…It was reported that the histological subtype of CRC in stage I is usually well-differentiated adenocarcinoma [32]. Especially, stage IV patients with poorly differentiated adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma (Por/Muc/Sig) had significantly shorter survival times than the patients with well-differentiated or moderately differentiated adenocarcinoma (Wel/Mod), indicating histological type as an independent prognostic factor for survival after recurrence [33,34]. In this study, histological subtypes in stage I were well-differentiated and moderately differentiated (low-grade, Wel 70% vs. Mod 30%) and those in stage IV were also lowgrade (Wel 40% vs. Mod 60%) ( Figure 6B, 5th column).…”

Section: Higher Levels Of Erbb4 and Kitenin Are Expressed Whereas A mentioning

confidence: 99%

KITENIN functions as a fine regulator of ErbB4 expression level in colorectal cancer via protection of ErbB4 from E3‐ligase Nrdp1‐mediated degradation

Sun

Lee

et al. 2016

Molecular Carcinogenesis

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Understanding the complex biological functions of E3-ubiquitin ligases may facilitate the development of mechanism-based anti-cancer drugs. We recently identified that the KITENIN/ErbB4-Dvl2-c-Jun axis works as a novel unconventional downstream signal of epidermal growth factor (EGF) in colorectal cancer (CRC) tissues. Here we addressed whether E3-ubiquitin ligases are required for operation of this axis. We found that Nrdp1, an E3-ligase for ErbB3/ErbB4, interacted with KITENIN (KAI1 C-terminal interacting tetraspanin) to form a functional KITENIN/ErbB4/Nrdp1 complex and is responsible for down-regulating Dvl2 within this complex. Interestingly, ErbB4 was resistant to degradation by Nrdp1 in KITENIN/Nrdp1-co-transfected CRC cells, and KITENIN bound to the C-terminal coiled-coil domain of Nrdp1. Chemical blockade of ErbB kinase did not block the action of EGF to increase in total/phospho-ErbB4 and phospho-ERK in KITENIN/ErbB4-cotransfected cells, whereas it blocked the action of EGF in ErbB4 alone-transfected CRC cells. In human CRC tissues, higher expressions of ErbB4 and KITENIN and lower expression of Dvl2 was observed in stage IV samples than in stage I, but a low level of Nrdp1 was expressed in both stages and it did not differ significantly by stage. These results indicated that Nrdp1 is necessary for the reduction in Dvl2 to generate c-Jun in the EGF-KITENIN/ErbB4-c-Jun axis, but more importantly, elevated KITENIN protects KITENIN-bound ErbB4 from Nrdp1-mediated degradation via physical collaboration between the KITENIN/ErbB4 complex and Nrdp1, but not via modulation of ErbB kinase activity. Thus, KITENIN functions in the maintenance of a higher expression level of ErbB4 in advanced CRC tissues, independent of ubiquitin-mediated degradation via Nrdp1. © 2016 Wiley Periodicals, Inc.

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Prognostic Impact of Histologic Type in Curatively Resected Stage IV Colorectal Cancer: A Japanese Multicenter Retrospective Study

Abstract: The patients with Por/Muc/Sig CRC synchronous metastasis had significantly shorter survival times than the patients with other CRC histologies, even if the metastases were curatively resected.

Cited by 10 publications

References 31 publications

Impact of sex and histology on the therapeutic effects of fluoropyrimidines and oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in the SOFT trial

Impact of sex and histology on the therapeutic effects of fluoropyrimidines and oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in the SOFT trial

Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare surgical value

KITENIN functions as a fine regulator of ErbB4 expression level in colorectal cancer via protection of ErbB4 from E3‐ligase Nrdp1‐mediated degradation

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