nach oben

International Journal of Clinical Oncology

Erschienen in:

11.01.2018 | Original Article

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer

verfasst von: Rin Yamada, Tatsuro Yamaguchi, Takeru Iijima, Rika Wakaume, Misato Takao, Koichi Koizumi, Tsunekazu Hishima, Shin-ichiro Horiguchi

Erschienen in: International Journal of Clinical Oncology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients.

Methods

Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.

Results

The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176).

Conclusions

Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Le DT, Uram JN, Wang H et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520CrossRefPubMedPubMedCentral

Peltomäki P, Lothe RA, Aaltonen LA et al (1993) Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res 53:5853–5855PubMed

Liu B, Parsons R, Papadopoulos N et al (1996) Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 2:169–174CrossRefPubMed

Herman JG, Umar A, Polyak K et al (1998) Incidence and functional consequences of MLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 95:6870–6875CrossRefPubMedPubMedCentral

Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268

Hartman DJ, Brand RE, Hu H et al (2013) Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach. Hum Pathol 44:2518–2528CrossRefPubMed

Rajagopalan H, Bardelli A, Lengauer C et al (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934CrossRefPubMed

Senter L, Clendenning M, Sotamaa K et al (2008) The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 135:419–428CrossRefPubMedPubMedCentral

Miyaki M, Iijima T, Yamaguchi T et al (2004) Both BRAF and KRAS mutations are rare in colorectal carcinomas from patients with hereditary nonpolyposis colorectal cancer. Cancer Lett 211:105–109CrossRefPubMed

10.

Young J, Simms LA, Biden KG et al (2001) Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol 159:2107–2116CrossRefPubMedPubMedCentral

11.

Jass JR, Walsh MD, Barker M et al (2002) Distinction between familial and sporadic forms of colorectal cancer showing DNA microsatellite instability. Eur J Cancer 38:858–866CrossRefPubMed

12.

Shia J, Ellis NA, Paty PB et al (2003) Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol 27:1407–1417CrossRefPubMed

13.

Yearsley M, Hampel H, Lehman A et al (2006) Histologic features distinguish microsatellite-high from microsatellite-low and microsatellite-stable colorectal carcinomas, but do not differentiate germline mutations from methylation of the MLH1 promoter. Hum Pathol 37:831–838CrossRefPubMed

14.

Droeser RA, Hirt C, Viehl CT et al (2013) Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer 49:2233–2242CrossRefPubMed

15.

Li Y, Liang L, Dai W et al (2016) Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer. Mol Cancer 15:55CrossRefPubMedPubMedCentral

16.

Rosenbaum MW, Bledsoe JR, Morales-Oyarvide V et al (2016) PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Mod Pathol 29:1104–1112CrossRefPubMed

17.

Lee LH, Cavalcanti MS, Segal NH et al (2016) Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol 29:1433–1442CrossRefPubMedPubMedCentral

18.

Inaguma S, Lasota J, Wang Z et al (2017) Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas. Mod Pathol 30:278–285CrossRefPubMed

19.

Lee KS, Kwak Y, Ahn S et al (2017) Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer. Cancer Immunol Immunother 66:927–939CrossRefPubMed

20.

Masugi Y, Nishihara R, Yang J et al (2017) Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut 66:1463–1473CrossRefPubMed

21.

Amaki-Takao M, Yamaguchi T, Natsume S et al (2016) Colorectal cancer with BRAF D594G mutation is not associated with microsatellite instability or poor prognosis. Oncology 91:162–170CrossRefPubMed

22.

Boland CR, Thibodeau SN, Hamilton SR et al (1998) A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMed

23.

Fujiyoshi K, Yamaguchi T, Kakuta M et al (2017) Predictive model for high-frequency microsatellite instability in colorectal cancer patients over 50 years of age. Cancer Med 6:1255–1263CrossRefPubMedPubMedCentral

24.

Ogino S, Kawasaki T, Brahmandam M et al (2006) Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis. J Mol Diagn 8:209–217CrossRefPubMedPubMedCentral

25.

Lee LH, Yantiss RK, Sadot E et al (2017) Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications. Hum Pathol 62:74–82CrossRefPubMed

26.

Väyrynen JP, Sajanti SA, Klintrup K et al (2014) Characteristics and significance of colorectal cancer associated lymphoid reaction. Int J Cancer 134:2126–2135CrossRefPubMed

27.

Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458CrossRefPubMed

28.

Alexander J, Watanabe T, Wu TT et al (2001) Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 158:527–535CrossRefPubMedPubMedCentral

29.

Hyde A, Fontaine D, Stuckless S et al (2010) A histology-based model for predicting microsatellite instability in colorectal cancers. Am J Surg Pathol 34:1820–1829CrossRefPubMed

30.

Hamilton SR, Bosman FT, Boffetta JM et al (2010) Medullary carcinoma. In: Bosman FT, Carneiro F, Hruban RH et al (eds) World Health Organization classification of tumours of the digestive system, 4th edn. IARC, Lyon, p 138

31.

Graham DM, Appelman HD (1990) Crohn’s-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Mod Pathol 3:332–335PubMed

32.

Ueno H, Hashiguchi Y, Shimazaki H et al (2013) Objective criteria for crohn-like lymphoid reaction in colorectal cancer. Am J Clin Pathol 139:434–441CrossRefPubMed

33.

Kim JH, Kim KJ, Bae JM et al (2015) Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma. J Clin Pathol 68:22–28CrossRefPubMed

34.

Song M, Chen D, Lu B et al (2013) PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer. PLoS One 8:e65821CrossRefPubMedPubMedCentral

35.

Shi SJ, Wang LJ, Wang GD et al (2013) B7-H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells. PLoS One 8:e76012CrossRefPubMedPubMedCentral

36.

Ilie M, Long-Mira E, Bence C et al (2016) Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol 27:147–153CrossRefPubMed

37.

Mansfield AS, Aubry MC, Moser JC et al (2016) Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Ann Oncol 27:1953–1958CrossRefPubMedPubMedCentral

38.

Madore J, Vilain RE, Menzies AM et al (2015) PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials. Pigment Cell Melanoma Res 28:245–253CrossRefPubMed

39.

Callea M, Albiges L, Gupta M et al (2015) Differential expression of PD-L1 between primary and metastatic sites in clear-cell renal cell carcinoma. Cancer Immunol Res 3:1158–1164CrossRefPubMedPubMedCentral

Titel: Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer
verfasst von: Rin Yamada
Tatsuro Yamaguchi
Takeru Iijima
Rika Wakaume
Misato Takao
Koichi Koizumi
Tsunekazu Hishima
Shin-ichiro Horiguchi
Publikationsdatum: 11.01.2018
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 3/2018
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-018-1238-y

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer

Abstract

Background

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2018

Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy

A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma

Prognostic value of the Glasgow Prognostic Score for patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy

No significant impact of response to prior androgen receptor-axis-targeted agents on the efficacy of subsequent docetaxel in patients with metastatic castration-resistant prostate cancer

Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: a review and update

Prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy: validation of Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score and impacts of pre-existing obesity and diabetes mellitus

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie