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. 2021 Aug 4;13(16):3928.
doi: 10.3390/cancers13163928.

CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients

Pierre Verrelle  1   2   3   4 , Didier Meseure  5   6 , Frédérique Berger  7 , Audrey Forest  1 , Renaud Leclère  5   6 , André Nicolas  5   6 , Emilie Fortas  5   6 , Xavier Sastre-Garau  8 , Marick Lae  9 , Sabah Boudjemaa  10 , Rodrigue Mbagui  4 , Valentin Calugaru  4 , Dalila Labiod  11 , Leanne De Koning  12 , Geneviève Almouzni  1 , Jean-Pierre Quivy  1
Affiliations

CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients

Pierre Verrelle et al. Cancers (Basel). .

Abstract

Effective biomarkers predictive of the response to treatments are key for precision medicine. This study identifies the staining pattern of the centromeric histone 3 variant, CENP-A, as a predictive biomarker of locoregional disease curability by chemoradiation therapy. We compared by imaging the subnuclear distribution of CENP-A in normal and tumoral tissues, and in a retrospective study in biopsies of 62 locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated by chemoradiation therapy. We looked for predictive factors of locoregional disease control and patient's survival, including CENP-A patterns, Ki67, HPV status and anisokaryosis. In different normal tissues, we reproducibly found a CENP-A subnuclear pattern characterized by CENP-A clusters both localized at the nuclear periphery and regularly spaced. In corresponding tumors, both features are lost. In locally advanced HNSCC, a specific CENP-A pattern identified in pretreatment biopsies predicts definitive locoregional disease control after chemoradiation treatment in 96% (24/25) of patients (OR = 17.6 CI 95% [2.6; 362.8], p = 0.002), independently of anisokaryosis, Ki67 labeling or HPV status. The characteristics of the subnuclear pattern of CENP-A in cell nuclei revealed by immunohistochemistry could provide an easy to use a reliable marker of disease curability by chemoradiation therapy in locally advanced HNSCC patients.

Keywords: biomarker; chemoradiation therapy; chromatin and nuclear organization; head and neck cancer; histological imaging.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
CENP-A staining by IHC in normal human tissues. Images of CENP-A staining by IHC in the indicated human tissues. Scale bar is 10 µm.
Figure 2
Figure 2
CENP-A staining by IHC in carcinomas reveals a pattern distinct from that of non-tumoral tissue. Images of CENP-A staining by IHC in non-Hodgkin lymphoma and carcinomas as indicated. Scale bar is 10 µm.
Figure 3
Figure 3
CENP-A localization patterns in breast lesions. Top: CENP-A staining by IHC in breast tissues as indicated. Invasive ductal carcinoma displaying CENP-A foci localized only inside the nuclear space (left) and a few remaining at the nuclear periphery (right) are shown. Scale bar is 10 µm. Bottom: scheme depicting the patterns.
Figure 4
Figure 4
CENP-A nuclear localization pattern is a marker of disease control by CCRT in HNSCC patients. (A) CENP-A IHC images of HNSCC biopsies corresponding to CENP-A pattern-C. Scale bar is 10 µm. A scheme depicting the pattern is shown on the right (B) as in (A), but for CENP-A pattern non-C. (C) Graph showing proportion (in %) of disease control in biopsies from patients displaying CENP-A pattern-C or non-C. (D) Kaplan–Meier survival curve of patients treated by CCRT with CENP-A pattern-C (black) and CENP-A pattern non-C (red).
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