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Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma

Tarhini, AA and Zahoor, H and Yearley, JH and Gibson, C and Rahman, Z and Dubner, R and Rao, UNM and Sander, C and Kirkwood, JM (2015) Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma. Journal of Translational Medicine, 13 (1).

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Abstract

© 2015 Tarhini et al. Background: Characterization of PD-L1 expression within clinically/radiologically negative but microscopically tumor positive sentinel lymph nodes (SLN) is important to our understanding of the relevance of this immune checkpoint pathway for adjuvant therapy. Methods: Patients included had primary cutaneous melanoma, Breslow thickness of 2.01-4.0 or >4mm with or without tumor ulceration (T3a, T3b, T4a, T4b). All patients had microscopically tumor positive SLN. Hematoxylin and eosin (H&E) staining was performed, followed by PD-L1 immunohistochemical (IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3. The slides were separately evaluated by two pathologists (JY and CG). Samples containing metastatic melanoma lesions were scored separately for PD-L1 expression in intratumoral and peritumoral locations, by utilizing two scoring methods. Results: Twenty-four patients where metastatic melanoma presence in the SLN was confirmed by H&E review of the cut sections were included in the final analysis of PD-L1 expression. SLN tumor size ranged from 1 to 2mm. For three patients, the melanin content was too high to confidently assign a PD-L1 score. For the remaining 21 patients, all had some evidence of either intratumoral or peritumoral PD-L1 expression. The frequency of intratumoral tumor-associated PD-L1 expression was: 0% of tumor cells (3pts, 14%); <1% (5pts, 24%); 1-10% (6pts, 29%) and >10% (7pts, 33%). Conclusions: Tumor-associated PD-L1 expression is readily detectable within melanoma micrometastases in the SLN of the majority of patients. These results support the testing of a therapeutic role for PD1/PD-L1 inhibition in the adjuvant setting, targeting melanoma micrometastases.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tarhini, AAaat8@pitt.eduAAT8
Zahoor, Hhaz42@pitt.eduHAZ42
Yearley, JH
Gibson, C
Rahman, Z
Dubner, R
Rao, UNMunr1@pitt.eduUNR1
Sander, Ccas32@pitt.eduCAS32
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Date: 30 September 2015
Date Type: Publication
Journal or Publication Title: Journal of Translational Medicine
Volume: 13
Number: 1
DOI or Unique Handle: 10.1186/s12967-015-0678-7
Schools and Programs: School of Medicine > Clinical Research
School of Medicine > Medicine
School of Medicine > Pathology
Refereed: Yes
Date Deposited: 05 Aug 2016 17:29
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/29140

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