Four immunohistochemical assays to measure the PD-L1 expression in malignant pleural mesothelioma

Our plain-English summary of Four immunohistochemical assays to measure the PD-L1 expression in malignant pleural mesothelioma, by T. Watanabe, K. Okuda, T. Murase, et al (Oncotarget, 2018).

The study

• Authors: T. Watanabe, K. Okuda, T. Murase, S. Moriyama, H. Haneda, O. Kawano, K. Yokota, T. Sakane, R. Oda, H. Inagaki, R. Nakanishi
• Journal: Oncotarget
• Published: 2018;9(29):20769-20780
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway are expected to be a novel therapy for combating future increases in numbers of malignant pleural mesothelioma (MPM) patients. However, the PD-L1 expression, which is a predictor of the response to ICIs, is unclear in MPM. We studied the PD-L1 expression using four immunohistochemical assays (SP142, SP263, 28-8 and 22C3) in 32 MPM patients. The PD-L1 expression in tumor cells and immune cells was evaluated to clarify the rate of PD-L1 expression and the concordance among the four assays in MPM. The positivity rate of PD-L1 expression was 53.1% for SP142, 28.1% for SP263, 53.1% for 28-8, and 56.3% for 22C3. Nine cases were positive and 10 were negative for all assays. Discordance among the four assays was found in 13 cases. The concordance rates between SP142 and 22C3 and between 28-8 and 22C3 were the highest (84.4%). The concordance rates between SP263 and the other three assays were low (71.9% to 75.0%). The PD-L1 expression in MPM was almost equivalent for three of the assays. Given the cut-off values set in our study, these findings suggested that these assays, except for SP263, can be used for accurate PD-L1 immunostaining in MPM.

In plain English

This Japanese study compared four tissue-staining tests (SP142, SP263, 28-8 and 22C3) for PD-L1, a protein used to predict response to immune checkpoint inhibitor drugs. The authors stained tumor tissue, collected 1992 to 2016, from 32 patients with malignant pleural mesothelioma (19 epithelial, 7 biphasic, 6 sarcomatous). Asbestos exposure was not studied. Tumor cells tested PD-L1 positive in 53.1% of cases with SP142, 28.1% with SP263, 53.1% with 28-8 and 56.3% with 22C3. Nine cases were positive and 10 negative on all four tests; the tests disagreed in 13 of 32 cases. Agreement was highest (84.4%) for SP142 with 22C3 and for 28-8 with 22C3, and lower (71.9% to 75.0%) between SP263 and each other test. SP142 counted a case positive at 1% staining of tumor cells or immune cells; SP263 required 25% of tumor cells; 28-8 and 22C3 required 1% of tumor cells. PD-L1 results were not significantly linked to tumor type or survival. The authors concluded that the three assays other than SP263 may suit PD-L1 staining in this disease. They named the small sample a major limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory comparison of four PD-L1 immunohistochemical assays on stored tumor tissue specimens, with review of medical records and survival analysis
• Who was studied: 32 patients with malignant pleural mesothelioma (27 male, 5 female; median age 60.5 years, range 34 to 79). Tumor types: 19 epithelial, 7 biphasic, 6 sarcomatous. Specimens were obtained from January 1992 to December 2016 at Nagoya City University Hospital, Japan, mostly surgical with two thoracoscopic biopsies. None came from patients given radiotherapy or chemotherapy before surgery.
• Exposure: No asbestos exposure was studied or reported for these patients. What the study compared was four anti-PD-L1 antibody assays (SP142, SP263, 28-8, 22C3). Positivity cut-offs were 1% tumor cells or 1% immune cells for SP142, 25% tumor cells for SP263, and 1% tumor cells for 28-8 and for 22C3.
• Main results:
  • Tumor-cell PD-L1 positivity across all 32 cases: 53.1% (17/32) with SP142, 28.1% (9/32) with SP263, 53.1% (17/32) with 28-8, and 56.3% (18/32) with 22C3
  • Immune cells showed markedly lower PD-L1 positivity rates than tumor cells
  • Nine cases (28.1%) were positive on all four assays and 10 (31.3%) were negative on all four. The assays disagreed in 13 of 32 cases (40.6%).
  • Agreement between assays was 84.4% for SP142 with 22C3 and for 28-8 with 22C3, and 81.3% for SP142 with 28-8. Agreement between SP263 and each of the other assays was 71.9% to 75.0%.
  • There was no statistically significant correlation between PD-L1 expression and tumor type (epithelial vs non-epithelial) with any assay
  • Overall survival did not differ significantly by PD-L1 status with any assay
  • When the SP263 cut-off was lowered to 1% of tumor cells, 4 of the 5 cases that had been negative only on SP263 became positive. SP263's overall positivity rate then rose to 46.9%.
• The authors' conclusion: The authors concluded that the three assays SP142, 28-8 and 22C3, at the cut-off values used in the study, may all be suitable for accurate PD-L1 staining in malignant pleural mesothelioma. They attributed SP263's lower positivity rate possibly to its cut-off value.
• Limitations the authors state:
  • The small number of samples was a major limitation. The authors suggested it was probably why no link with prognosis was found.
  • Almost all specimens were surgical and untreated. Including more biopsy specimens taken after treatment might have given different results.
  • The use of non-standardized immunohistochemical techniques might have affected the results

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, checkpoint inhibitors, PD-1/PD-L1.

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