Histol Histopathol

Original Article Open Access

Stroma composition and proliferative activity are related to therapy response in neoadjuvant treated pancreatic ductal adenocarcinoma

Lena Haeberle1*, Andrea Cacciato Insilla2*, Anne-Christine Kapp3, Katja Steiger4, Anna Melissa Schlitter4, Björn Konukiewitz4, Ihsan Ekin Demir5, Helmut Friess5 and Irene Esposito1

1Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Germany, 2Department of Surgical, Medical, Molecular and Critical Care Pathology, University of Pisa, Pisa, Italy, 3Department of Anesthesiology, University Hospital of Heidelberg, Heidelberg, Germany, 4Institute of Pathology, Technical University of Munich, Germany and 5Department of General Surgery, Klinikum Rechts der Isar, School of Medicine Technical University Munich, Munich, Germany
*Authors contributed equally


Corresponding Author: Irene Esposito, MD, Institute of Pathology, Heinrich-Heine University and University Hospital of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany. e-mail: irene.esposito@med.uni-duesseldorf.de


Summary. Background. Tumor regression grading (TRG) based on histopathology is the main tool to assess therapy effects after neoadjuvant therapy (NAT) of pancreatic ductal adenocarcinoma (PDAC). However, reliable markers to distinguish therapy effects from pre-existing tumor features are lacking. The aim of this study was the characterization of PDAC after NAT, focusing on the stroma.
Material and Methods. Tissue samples from patients resected for PDAC after NAT (n=27) were analyzed. TRG was assessed using the Royal North Shore (RNS) system. Stromal composition was evaluated by Movat's stain. Immunohistochemistry (IH) for Ki-67 and five previously established stroma markers (alpha-Crystallin B, alpha-Smooth muscle actin (alpha-SMA), Neurotrophin-3 (NT-3), SPARC and Tenascin C) was also performed. Results were compared with therapy-naïve PDACs (n=10).
Results. Most cases showed a moderate response (RNS 2; 74%), while 15% displayed a poor response (RNS 3), and 11% a good response (RNS 1). No complete response was observed. Poor regression was associated with mucin-rich stroma, while good regression was associated with collagen-rich stroma. Cases with poorer therapy response had significantly higher proliferation. Higher peritumoral staining intensity for alpha-SMA and Tenascin C also showed a trend towards an association with poor regression.
Conclusions. Similar to the stroma in therapy-naïve PDAC, the stroma of PDAC after NAT is heterogeneous. Distinguishing between desmoplastic stroma and therapy-induced fibrosis by single markers is not possible. Movat's pentachrome stain, IH for Ki-67, and to some extent for Tenascin C and alpha-SMA, can help detect poor histopathological response to NAT. Histol Histopathol 36, 733-742 (2021)

Key words: Movat's stain, Neoadjuvant therapy, Pancreatic cancer, Proliferation, Stroma, Tumor regression grading

DOI: 10.14670/HH-18-332


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©The Author(s) 2021. Open Access. This article is licensed under a Creative Commons CC-BY International License.