Microsatellite Instability-high Intrahepatic Cholangiocarcinoma with Portal Vein Tumor Thrombosis Successfully Treated with Pembrolizumab

Naganuma, Atsushi; Sakuda, Takayoshi; Murakami, T.; Aihara, Kosuke; Watanuki, Yuta; Suzuki, Yuhei; Shibasaki, Erina; Masuda, Tomoyuki; Uehara, Sanae; Yasuoka, Hidetoshi; Hoshino, Takashi; Kudo, Toshifumi; Ishiguro, Hiroshi; Ogawa, Tetsushi; Kitamoto, Yoshizumi

doi:10.2169/internalmedicine.4588-20

Cited by 20 publications

(10 citation statements)

References 21 publications

(23 reference statements)

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“…Recently, it has been reported that immune checkpoint inhibitor (pembrolizumab) was effective in MSI-H patients with tumor thrombosis. This re ects the relationship between tumor thrombus and MSI and tumor immune microenvironment (31). Consistent with the previously studies, we found that CTNNA3 and FRMPD4 were positively correlated with MSI, as well as with immune microenvironment and immune cell subtype in ltration.…”

Section: Discussionsupporting

confidence: 92%

Potential Role of CTNNA3 and FRMPD4 in Vascular Thrombosis of Colon Adenocarcinoma

Liu

Guo

2021

Preprint

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Background: Vascular tumor thrombus is an important pathological feature of malignant tumors, closely related to lymph node metastasis, and considered to be tumor micrometastasis. Two down-regulated genes, Catenin Alpha 3 (CTNNA3) and FERM And PDZ Domain Containing 4 (FRMPD4) were selected via analyzing the differential expression of vascular tumor thrombus in colon adenocarcinoma and paracancerous tissues. Furthermore, we observed the potential role of them in vascular thrombosis of colon adenocarcinoma.Method: Candidate genes for vascular thrombosis of colon adenocarcinoma were screened by GSE127069, and then pan-cancer verification and immune infiltration analysis were performed. The relationship between gene and vascular thrombosis was analyzed from the level of gene mutation by cBioPortal. Finally, the clinical samples collected were used for expression verification.Results: CTNNA3 and FRMPD4 were low-expressed in vascular tumor thrombus of colon adenocarcinoma, which were positively correlated with microsatellite instability (MSI). They were also closely related to immune microenvironment and immune cell subtype infiltration. According to the analysis of gene mutation, their gene deletion was related to the vascular invasion indicator. Finally, the protein and mRNA expression of CTNNA3 and FRMPD4 were down-regulated in the samples of vascular thrombosis of colon adenocarcinoma, compared with the normal glands which from paracancerous tissues.Conclusion: Our study demonstrates that CTNNA3 and FRMPD4 may be potential biomarkers of vascular thrombosis in colon adenocarcinoma. These results may provide a new strategy to identify the micrometastasis in colon adenocarcinoma.

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Section: Discussionsupporting

confidence: 92%

Potential Role of CTNNA3 and FRMPD4 in Vascular Thrombosis of Colon Adenocarcinoma

Liu

Guo

2021

Preprint

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“…Few cholangiocarcinoma cases have reported response to pembrolizumab; however, these tumors were microsatellite unstable or mismatch repair genes (MMR) deficient and only one case achieved pCR with pembrolizumab treatment alone [15][16][17][18]. Conversely, our patient was pMMR and MSS but TMB-H. TMB has emerged as an independent predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated, recurrent, or metastatic advanced solid tumors [19,20].…”

Section: Discussionmentioning

confidence: 66%

Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in a Patient With Metastatic Intrahepatic Cholangiocarcinoma With High Tumor Mutational Burden

Abudalou¹,

Vega²,

Kondratiev³

et al. 2021

Cureus

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Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary tract cancer (BTC) with distinct anatomic, molecular, and clinical characteristics. Over the last 10-20 years, ICC has become the focus of increasing concern largely due to its rising incidence and high mortality rates in various parts of the world, including the United States.Surgery is the only potentially curative treatment option for ICC; however, recurrence rate is high, and prognosis is poor in patients with recurrent disease. The chemotherapy regimen of gemcitabine-cisplatin (GemCis) is still the standard of care for patients with unresectable metastatic ICC. There is limited data regarding pathologic ICC response to palliatively intentioned systemic treatment.Here, we report a case of a 47-year-old Caucasian male with metastatic ICC microsatellite stable (MSS) and TMB 49 mutation per megabase who achieved complete pathological response with sequential GemCis/nabpaclitaxel and pembrolizumab. This case highlights the effect of sequential neoadjuvant chemoimmunotherapy in a patient with high tumor mutational burden (TMB-H) ICC, emphasizing the importance of molecular testing, which provides valuable information that can be used in clinical practice to better select targeted chemotherapy regimens.

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“…Only three case reports exist of MSI‐high advanced cholangiocarcinoma treated with pembrolizumab 9‐11 . All cases showed a good response and maintained a PR during pembrolizumab treatment.…”

Section: Discussionmentioning

confidence: 99%

Successful pembrolizumab treatment of microsatellite instability‐high intrahepatic cholangiocarcinoma: A case report

Ikeda

Ono

Ohmori

et al. 2021

Clinical Case Reports

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Microsatellite Instability-high Intrahepatic Cholangiocarcinoma with Portal Vein Tumor Thrombosis Successfully Treated with Pembrolizumab

Cited by 20 publications

References 21 publications

Potential Role of CTNNA3 and FRMPD4 in Vascular Thrombosis of Colon Adenocarcinoma

Potential Role of CTNNA3 and FRMPD4 in Vascular Thrombosis of Colon Adenocarcinoma

Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in a Patient With Metastatic Intrahepatic Cholangiocarcinoma With High Tumor Mutational Burden

Successful pembrolizumab treatment of microsatellite instability‐high intrahepatic cholangiocarcinoma: A case report

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