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Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma

  • Authors:
    • Mark Zupancic
    • Madeleine Birgersson
    • Signe Friesland
    • Tina Dalianis
    • Anders Näsman
  • View Affiliations / Copyright

    Affiliations: Department of Oncology‑Pathology, Karolinska Institute, Bioclinicum, Karolinska University Hospital, 171 64 Stockholm, Sweden
    Copyright: © Zupancic et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 17
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    Published online on: January 27, 2026
       https://doi.org/10.3892/mco.2026.2926
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Abstract

Adenoid cystic carcinoma (AdCC) evolves from the salivary glands and may arise in the head and neck region or outside of this area. The symptoms of AdCC are generally nonspecific, and its diagnosis is challenging due to its heterogeneous histopathology and indolent growth. Moreover, reliable prognostic markers are lacking. Therefore, the present study investigated the prognostic potential of immunohistochemical staining of the immune markers HLA class I, CD4, CD8 and FOXP3 in AdCC. In total, 72 patients diagnosed with AdCC between January 2000, and December 2014 were included. Biopsy material underwent immunohistochemical staining for the aforementioned markers, and staining extent and intensity in the tumour and corresponding stroma were assessed, and their association with clinical outcome was investigated. Patients with analogous staining intensity of HLA class I in the tumour tissue to that in the stromal tissue had significantly fewer recurrences, as compared with those with lower HLA class I intensity staining in the tumour than in the stroma. By contrast, CD8+, CD4+ and FOXP3+ staining was not significantly associated with recurrence. Furthermore, none of the markers were associated with overall survival. Moreover, patients with clinical stage I and II had fewer recurrences than those with stage III and IV AdCC. In conclusion, among the investigated biomarkers, only an analogous HLA class I expression in tumour tissue relative to that in the stromal tissue was associated with a reduced risk of recurrence in AdCC. These findings suggest a potential role of HLA class I as a prognostic marker in this rare malignancy.

View Figures

Figure 1

Different presentations of HLA class I
using immunohistochemistry. HLA-I staining revealing differential
expression patterns with an analogous intensity staining in tumour
compared to the stroma (left) or a lower intensity HLA class I
staining in the tumour compared to the stroma (right).
Magnification: x20, scale bar (white): 50 µM.

Figure 2

Kaplan Meier curves illustrating (A)
DFS and (B) OS in patients with tumours showing HLA class I equal
to the surrounding stroma (black line) or lower than that observed
in stroma (grey line). For DFS, 5-year survival was 63% vs. 54%,
and 10-year survival was 60% vs. 29% (log-rank test: P=0.048). For
OS, 5-year survival was 88% vs. 75%, and 10-year survival was 50%
vs. 30% (log-rank test: P=0.10). DFS, disease-free survival; IHC,
immunohistochemistry; OS, overall survival.

Figure 3

Expression of T-cell markers in
adenoid cystic carcinoma. Immunohistochemistry staining of CD8 in
the (A) tumour and (B) stroma. Immunohistochemistry staining of CD4
in the (C) tumour and (D) stroma. Immunohistochemistry staining of
FOXP3 in the (E) tumour and (F) stroma. Numbers indicate cell
number per 1 mm3, thereby illustrating examples of
tissues with higher or lower concentrations of the corresponding
stained cells. Magnification: x20, scale bar (white): 50 µM.
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Spandidos Publications style
Zupancic M, Birgersson M, Friesland S, Dalianis T and Näsman A: <p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>. Mol Clin Oncol 24: 17, 2026.
APA
Zupancic, M., Birgersson, M., Friesland, S., Dalianis, T., & Näsman, A. (2026). <p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>. Molecular and Clinical Oncology, 24, 17. https://doi.org/10.3892/mco.2026.2926
MLA
Zupancic, M., Birgersson, M., Friesland, S., Dalianis, T., Näsman, A."<p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>". Molecular and Clinical Oncology 24.3 (2026): 17.
Chicago
Zupancic, M., Birgersson, M., Friesland, S., Dalianis, T., Näsman, A."<p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>". Molecular and Clinical Oncology 24, no. 3 (2026): 17. https://doi.org/10.3892/mco.2026.2926
Copy and paste a formatted citation
x
Spandidos Publications style
Zupancic M, Birgersson M, Friesland S, Dalianis T and Näsman A: <p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>. Mol Clin Oncol 24: 17, 2026.
APA
Zupancic, M., Birgersson, M., Friesland, S., Dalianis, T., & Näsman, A. (2026). <p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>. Molecular and Clinical Oncology, 24, 17. https://doi.org/10.3892/mco.2026.2926
MLA
Zupancic, M., Birgersson, M., Friesland, S., Dalianis, T., Näsman, A."<p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>". Molecular and Clinical Oncology 24.3 (2026): 17.
Chicago
Zupancic, M., Birgersson, M., Friesland, S., Dalianis, T., Näsman, A."<p>Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma</p>". Molecular and Clinical Oncology 24, no. 3 (2026): 17. https://doi.org/10.3892/mco.2026.2926
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