The expression of programed death ligand‐1 could be related with unfavorable prognosis in salivary duct carcinoma

Satô, Fumihiko; Akiba, Jun; Kawahara, Akihiko; Naito, Yoshiki; Ono, Takeharu; Takase, Yoshiaki; Murata, Kazuya; Abe, Hideyuki; Yamaguchi, Tomohiko; Miyoshi, Hiroaki; Abe, Yushi; Mihara, Yutaro; Tanikawa, Masahiko; Akashi, Momoko; Kurose, Hirofumi; Umeno, Hirohito; Yano, Hirohisa

doi:10.1111/jop.12722

Cited by 30 publications

(27 citation statements)

References 29 publications

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“…Five of our cases exhibited low level (1%‐8%) PD‐L1 expression in tumor cells. A recent study by Sato et al, which utilized the PD‐L1 clone E1L3N (Cell Signaling Technology), revealed higher rates of PD‐L1 expression in SDC tumor cells, with 4 of 18 cases showing high expression (defined as greater than 10%) and 5 of 18 cases showing low expression (1%‐9%); moreover high PD‐L1 expression strongly correlated with shorter overall survival. In our study, two different anti‐PD‐L1 assays (laboratory developed SP142 assay and 28‐8 complementary diagnostic assay used for head and neck squamous cell carcinoma) were used in 2 different groups of cases, respectively.…”

Section: Discussionmentioning

confidence: 98%

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

et al. 2019

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Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%‐8%) programmed death ligand 1 (PD‐L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre‐treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti‐androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD‐L1, mitogen‐activated protein kinase, and PIK3CA pathways.

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Section: Discussionmentioning

confidence: 98%

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

et al. 2019

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“…There are a few differences between our study and the two previously mentioned studies [13,19]. Firstly, we did not stratify the PD-L1 expression into high and low; and simply considered immunoreactivity of ≥ 1% as positive.…”

Section: Discussionmentioning

confidence: 87%

“…In a recent study of recurrent or metastatic salivary gland carcinomas with PD-L1 expression in ≥1% of tumor or stromal cells, pembrolizumab demonstrated some anti-tumor activity, with a confirmed objective response rate of 12% (95% confidence interval, 2%−30%) after a median followup of 20 months [18]. With respect to SDC only, a recent study of 18 patients found that high PD-L1 expression (defined in the study by positivity in > 10% of tumor cells) was strongly associated with unfavorable prognosis and shorter overall survival (log-rank test: p = .0045) [19]. In a study of 219 salivary gland tumors, which included 31 cases of SDC, PD-L1 expression was associated with reduced 5 year disease free survival as well as overall survival (p = < 0.001) [13].…”

Section: Discussionmentioning

confidence: 93%

“…We used the 22C3 and 28-8clones in our study; Mukaigawa et al [13] and Sato et al [15] both used clone E1L3N. We and Mukaigawa et al [13] used tissue microarrays, while whole tissue sections were used by Sato et al [19]. Another factor that may have contributed to the low level of PD-L1 positivity may be use of the TMAs rather than whole tissue sections; however, Mukaigawa et al [13] also used TMAs and about 50% of their cases demonstrated staining.…”

Section: Discussionmentioning

confidence: 99%

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PD-L1 expression by immunohistochemistry in salivary duct carcinoma

Hamza

Roberts

et al. 2019

Annals of Diagnostic Pathology

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Background: Immune checkpoint inhibitors play an increasing role in oncologic care. PD-L1 expression is associated with survival and predicts response to PD-1 or PD-L1 inhibitors in a variety of tumors. Our aim is to evaluate the frequency and prognostic significance of PD-L1 expression in salivary duct carcinoma. Design: We retrospectively evaluated the expression of PD-L1 by two different antibodies (PD-L1 28-8 and PD-L1 22C3) in salivary duct carcinomas. PD-L1 expression in at least 1% of tumor cells was considered immunoreactive. Kaplan-Meier analysis was performed to determine the impact of PD-L1 expression on survival; differences between survival curves were assessed by the chi-square test, and pairwise comparisons factor were assessed with the log-rank test. Results: A total of 113 patients' specimens were evaluated. Seventy-six (76%) of the patients were male. Mean age at time of presentation was 61.2 (SD = 12.4) years. PD-L1 expression was found in 26% of the samples. Median follow-up time was 36.6 months (range = 1.4-249). Overall survival at 3, 5 and 10 years were 52.6%, 37.9% and 25.6%, respectively. There was no statistical difference in survival between patients with PD-L1-immunoreactive tumors and those without, regardless of which antibody was used (chi 2 result for all plots: p = 0.53; log rank test for pairwise comparison: p > 0.256). Conclusion: In our analysis, PD-L1 expression occurred in a small proportion of salivary duct carcinomas, usually at low levels, and did not correlate with survival. Its predictive value and utility in selecting patients who might benefit from PD-1/PD-L1 inhibitors in salivary duct carcinoma warrants further investigation.

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“…Most SDC cases are microsatellite‐stable and have a low TMB 59,63,70,73,82 . There are no consistent data on PD‐L1 expression 59‐64 . A study of immune checkpoint inhibitor (pembrolizumab) treatment for advanced salivary gland carcinoma reported a 12% response rate, and another study of pembrolizumab included 1 SDC case in the cohort 109,110 .…”

Section: Treatmentmentioning

confidence: 99%

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment

Nakaguro

Tada

Faquin

et al. 2020

Cancer Cytopathology

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Salivary duct carcinoma (SDC) is an aggressive subtype of primary salivary gland carcinoma, often with an advanced stage at presentation and high rates of metastasis and recurrence. It most commonly arises in the parotid gland of older men and microscopically resembles high-grade breast ductal carcinoma. While 50 years have lapsed since the first report of this entity, recent intensive studies have shed light on its biologic, genetic, and clinical characteristics. The diagnosis of SDC is aided by the immunohistochemical expression of androgen receptor (AR) coupled with its characteristic histomorphology. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma, and ancillary studies using cell block material can facilitate the specific diagnosis of SDC. In surgical specimens, certain histologic features are important prognostic factors, including nuclear pleomorphism, mitotic counts, vascular invasion, and the morphology at the invasion front. Several clinical studies have shown promising results using targeted therapy for AR and human epidermal growth factor receptor 2 (HER2), and the latest version of the National Comprehensive Cancer Network guidelines recommends the evaluation of AR and HER2 status before treatment. Recent molecular analyses have revealed multiple heterogeneous alterations in wellknown oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF. Clinical trials of drugs targeting these genes may broaden the treatment options for SDC in the near future.

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The expression of programed death ligand‐1 could be related with unfavorable prognosis in salivary duct carcinoma

Abstract: High PD-L1 expression in SDC was strongly associated with unfavorable prognosis, indicating that PD-1/PD-L1 inhibitors could be effective in SDC.

Cited by 30 publications

References 29 publications

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

PD-L1 expression by immunohistochemistry in salivary duct carcinoma

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment

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