Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells

Lehrke, Heidi D.; Graham, Rondell P.; McWilliams, Robert R.; Lam-Himlin, Dora; Smyrk, Thomas C.; Jenkins, Sarah M.; Dong, Haidong; Zhang, Lizhi

doi:10.1093/ajcp/aqx092

Cited by 23 publications

(36 citation statements)

References 41 publications

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“…Overexpression of autophagy-related proteins is evident in UC with rhabdoid features [100]. Prevalence of programmed cell death ligand 1 expression in UC/ UCOGC (63%) is greater than in DA (15%) [102]. Based on the present study, it may be presumed that TAp63 upregulation is another event during dedifferentiation of DA to UC.…”

Section: Biological Features Of Uc/ucogc Of the Pancreassupporting

confidence: 47%

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

Liszka

2020

pjp

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Undifferentiated carcinoma of the pancreas (UC) is a carcinoma without a definitive direction of differentiation. Tumour protein p63 is a regulator of squamous phenotype, which may also be engaged in tumour development. N-terminal isoforms of p63 are TAp63 and ΔNp63. Pan-p63 antibodies are able to detect both isoforms, whereas p40 antibodies recognise the ΔNp63 isoform only. The aim of the study was to describe pan-p63/p40 immunohistochemical expression patterns in pancreatic neoplasms: UC, ductal adenocarcinomas, neuroendocrine tumours, neuroendocrine carcinomas, serous cystic neoplasms, and solid pseudopapillary neoplasms. DAK-p63 and BC28 antibodies were used for pan-p63 and p40 detection, respectively. Moderate-to-strong pan-p63 was found in anaplastic (pleomorphic giant cell) UC (n = 4), sarcomatoid UC (n = 2), UC with osteoclast-like giant cells (n = 3), and ductal carcinomas with partial squamous differentiation. Weak and focal pan-p63 expression was found in monomorphic UC (n = 3) and in the majority of neuroendocrine carcinomas (6/7 cases). Pan-p63 expression was infrequent in ductal carcinomas without squamous differentiation and in neuroendocrine tumours. Serous cystic and solid pseudopapillary neoplasms were pan-p63-negative. Ductal carcinomas with partial squamous differentiation were the only tumours with evident p40 expression. Pan-p63(+)/p40(-) immunohistochemical status may be supportive for UC diagnosis. The pan-p63 expression was not equivalent to squamous differentiation in pancreatic neoplasia.

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Section: Biological Features Of Uc/ucogc Of the Pancreassupporting

confidence: 47%

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

Liszka

2020

pjp

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“…In univariate analysis, patients with PD-L1-positive UCOGC had a risk of all-cause mortality that was more than 4-times that of PD-L1-negative UCOGC There was only one statistically significant association derived from the comparison of the expression of PD-L1, PD-1, and CD163 with the molecular data from our previous molecular analysis study of UCOGCs [7]. We identified a expression in this study [24]. In this study, 24 undifferentiated carcinomas were analyzed, but only 5 were UCOGCs; 4 out of 5 UCOGCs were PD-L1 positive [24].…”

Section: Accepted Manuscriptmentioning

confidence: 58%

“…We identified a expression in this study [24]. In this study, 24 undifferentiated carcinomas were analyzed, but only 5 were UCOGCs; 4 out of 5 UCOGCs were PD-L1 positive [24].…”

Section: Accepted Manuscriptmentioning

confidence: 89%

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PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications

et al. 2018

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Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) of 27 cases, more often in cases with an associated PDAC (P = .04). Expression of PD-L1 was associated with poor prognosis, confirmed by multivariate analysis: patients with PD-L1-positive UCOGCs had a risk of all-cause mortality that was 3 times higher than did patients with PD-L1-negative UCOGCs (hazard ratio, 3.397; 95% confidence interval, 1.023-18.375; P = .034). PD-L1 expression on tumor cells was also associated with aberrant P53 expression (P = .035). PD-1 was expressed on rare lymphocytes in 12 UCOGCs (44.4%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extrapancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. Anaplastic carcinomas have some similarities to UCOGCs, but PD-L1 has no prognostic roles. Our results may have important implications for immunotherapeutic strategies in UCOGCs; these tumors may also represent a model for future therapeutic approaches against PDAC.

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“…The pleomorphic giant cell subtype displays KRAS alterations with preservation of SMARCB1 expression; in contrast, the anaplastic monomorphic subtype shows absence of KRAS alterations with loss of SMARCB1 expression. To our best knowledge, eight SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinomas have been reported in the literature[ 2 - 6 ]. Our case is the first reported case with a solid and pseudopapillary growth pattern mimicking solid pseudopapillary neoplasm (SPN).…”

Section: Introductionmentioning

confidence: 99%

SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma mimicking solid pseudopapillary neoplasm: A case report and review of the literature

Hua¹,

Soni²,

Larsen³

et al. 2020

WJG

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BACKGROUND SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma is a very aggressive tumor that is rarely reported in the literature. The tumor has a predominant rhabdoid cell component and different patterns of growth have been reported. CASE SUMMARY A 59-year-old woman presented with diffuse abdominal pain, increasing in severity and accompanied by weight loss, nausea, and vomiting. Imaging showed a pancreatic head mass. Fine needle aspiration demonstrated atypical epithelioid cells with a pseudopapillary growth pattern suggestive of solid pseudopapillary neoplasm. The excised neoplasm showed monotonous epithelioid and focally spindle cells with pseudopapillary structures, rhabdoid features, and loss of SMARCB1 protein expression with wild-type KRAS , consistent with a SMARCB1/INI1-deficient undifferentiated rhabdoid carcinoma. The patient’s condition deteriorated rapidly following surgery and she expired 3 mo post operation. CONCLUSION In this article, we report the first case of SMARCB1/INI1-deficient undifferentiated pancreatic rhabdoid carcinoma mimicking solid pseudopapillary neoplasm.

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Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells

Abstract: UPC is enriched for PD-L1 expression in frequency and extent, relative to conventional PDA. Anti-PD-1/PD-L1 agents may represent a valuable therapeutic approach for this subset of highly aggressive pancreatic carcinoma.

Cited by 23 publications

References 41 publications

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications

SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma mimicking solid pseudopapillary neoplasm: A case report and review of the literature

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