A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine

Herfs, Michaël; Roncarati, Patrick; Koopmansch, Benjamin; Peulen, Olivier; Bruyère, Diane; Lebeau, Alizée; Hendrick, Elodie; Hubert, Pascale; Poncin, Aurélie; Penny, W. M.; Piazzon, Nathalie; Monnien, Franck; Guenat, David; Mougin, Christiane; Prétet, Jean‐Luc; Vuitton, Lucine; Segers, Karin; Lambert, Frédéric; Leval, Laurence de; Valmary‐Degano, Séverine; Quick, Charles M.; Crum, Christopher P.; Delvenne, Philippe

doi:10.1038/s41416-018-0049-2

Cited by 33 publications

(29 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, IFN-γ, produced by TILs, seems not to be the main reason for the difference of PD-L1 expression between HPV positive and negative anogenital cancer patients, because no signi cant difference was identi ed in numbers of CD8 + TILs distributing in HPV positive and negative anal and cervical cancer patients [38,39]. In vulvar SCC, there was fewer number of CD8 + TILs in p16 positive cases compared with p16 negative [40].…”

Section: Discussionmentioning

confidence: 94%

PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis

Yuan

Luan

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundLittle research has been done on clinicopathological characteristics and human papillomavirus (HPV) status of anogenital and oropharyngeal squamous cell carcinomas (SCC) with a strong expression of programmed death ligand 1 (PD-L1) in tumor cells. Therefore, we conducted this meta-analysis.MethodsWe performed a comprehensive research in PubMed, Embase and Cochrane databases up to September 30th, 2019. The effect size was hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), cancer specific survival (CSS), disease free survival (DFS). The pooled odds ratio (OR) with 95%CI were used to assess the association between PD-L1 expression and clinicopathological features along with HPV status.ResultsA total of 2003 cases (944 anogenital and 1059 oropharynx SCC patients) were included. High PD-L1 expression in anogenital SCC cases were associated with advanced age (OR=1.63, 95%CI:1.04-2.58) and HPV negativity (OR=0.47,95%CI:0.31-0.71). Besides, PD-L1 positive anogenital SCC cases held a significant declined OS (HR=2.18, 95%CI:1.37-3.47) and CSS (HR=2.45, 95%CI:1.30-4.65). For oropharynx SCC, PD-L1 was more frequent in younger and HPV positive patients (OR=0.60, 95%CI:0.37-0.98; OR=3.01, 95%CI:1.78-5.09) and PD-L1 expression was relevant to better OS and DFS (HR=0.76, 95%CI:0.60-0.97; HR=0.50, 95%CI:0.33-0.75).ConclusionsThe meta-analysis demonstrated that in anogenital SCC, PD-L1 positivity had to do with a worse outcome, which might attribute to advanced age, higher tumor grade, lymph node metastasis and HPV negativity, while in oropharynx cancer, PD-L1expression was related to better prognosis for the reason that PD-L1 was less frequent in the aged and negative HPV status.

show abstract

Section: Discussionmentioning

confidence: 94%

PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis

Yuan

Luan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Increasing evidence shows that numerous lymphocytes infiltrate tumor tissues to inhibit tumor growth and metastasis [22, 23]. Therefore, evading killing by immune cells is one of the key factors driving tumor cell survival.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway

Cui

Yang

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. Methods Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2 -targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. Results HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2 -silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. Conclusion The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.

show abstract

“…This patient did not have certain sexual history and had KRAS-mutant tumor. Although we did not evaluate HPV infection in this case, the carcinogenesis of this patient seemed to be less associated with HPV infection [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Histological findings are usually squamous cell carcinoma and the remaining including adenocarcinoma, neuroendocrine carcinoma (NEC), melanoma, lymphoma, undifferentiated carcinoma, and mesenchymal tumors [ 5 , 6 ]. Anal canal adenocarcinoma is less associated with HPV infection [ 7 ] and divided into two subtypes according to the presence of mutations in EGFR signaling pathway and expression of the immune checkpoint molecules [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report

et al. 2018

View full text Add to dashboard Cite

BackgroundAnal canal cancer occasionally accompanies extramammary Paget disease. Although most of them are squamous cell carcinoma, anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease has never been reported.Case presentationHere, we report a 76-year-old man presented with pruritus in the perianal area. Investigation revealed a fist-sized perianal erythema, diffuse liver tumors, and right inguinal lymph node swelling. Pathological examination of biopsies from the erythema suggested secondary extramammary Paget disease with positive cytokeratin-7 and -20 expressions and negative GCDFP-15 expression. The anal canal tumor was confirmed by digital examination and endoscopy. Biopsies from the anal canal tumor, swollen lymph node, and Paget lesion all showed poorly differentiated adenocarcinoma with neuroendocrine features expressing synaptophysin and chromogranin A. Serum CEA and NSE levels were high, 809.4 ng/ml and 85.8 ng/ml, respectively. After chemotherapy with modified FOLFOX6 for 2 months, the Paget lesion disappeared, and the primary anal canal tumor and liver metastases shrunk remarkably. Serum CEA and NSE levels decreased promptly to within normal ranges.ConclusionsThis is a clinically significant case, as it reveals novel pathological features about anal canal cancer with secondary Paget disease and successfully treated with modified FOLFOX6. Careful pathological investigation and appropriate treatment choice are needed for this rare cancer.

show abstract

A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine

Cited by 33 publications

References 53 publications

PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis

PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis

Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway

Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report

Contact Info

Product

Resources

About