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2.
Data Brief ; 44: 108556, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36111282

RESUMEN

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.

3.
Eur J Cancer ; 174: 287-298, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36038492

RESUMEN

INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Cetuximab/uso terapéutico , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Fenotipo , Receptor de Muerte Celular Programada 1/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética
4.
Mol Oncol ; 16(16): 3001-3016, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35398964

RESUMEN

A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.


Asunto(s)
Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Carcinogénesis , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , ADN , Genómica , Neoplasias de Cabeza y Cuello/genética , Humanos , Factores de Transcripción de Tipo Kruppel , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética
5.
Genes Chromosomes Cancer ; 61(6): 382-393, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35080790

RESUMEN

Many neoplasms remain unclassified after histopathological examination, which requires further molecular analysis. To this regard, mesenchymal neoplasms are particularly challenging due to the combination of their rarity and the large number of subtypes, and many entities still lack robust diagnostic hallmarks. RNA transcriptomic profiles have proven to be a reliable basis for the classification of previously unclassified tumors and notably for mesenchymal neoplasms. Using exome-based RNA capture sequencing on more than 5000 samples of archival material (formalin-fixed, paraffin-embedded), the combination of expression profiles analyzes (including several clustering methods), fusion genes, and small nucleotide variations has been developed at the Centre Léon Bérard (CLB) in Lyon for the molecular diagnosis of challenging neoplasms and the discovery of new entities. The molecular basis of the technique, the protocol, and the bioinformatics algorithms used are described herein, as well as its advantages and limitations.


Asunto(s)
Neoplasias , Transcriptoma , Formaldehído , Perfilación de la Expresión Génica/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Adhesión en Parafina/métodos , ARN , Fijación del Tejido/métodos , Transcriptoma/genética
6.
Oral Oncol ; 119: 105368, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34111704

RESUMEN

BACKGROUND: Programmed death-ligand 1 (PD-L1) is the most validated predictive biomarker used for the treatment of head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (ICI). Several gene expression-based signatures surrogate of the activation of IFN-gamma pathway and of the presence of tertiary lymphoid structures (TLS) have also been proposed as potential biomarkers. While they may have a potential therapeutic implication, the longitudinal changes of either PD-L1 or gene expression profiles between the initial and recurrent HNSCC lesions is unknown. METHODS: PD-L1 immunohistochemistry (IHC) and targeted RNA-sequencing of 2,549 transcripts were analyzed on paired specimens from the initial diagnosis and recurrent HNSCC. PD-L1 status was defined using the combined positive score (CPS). PD-L1 mRNA levels were compared with protein expression levels by IHC. Enrichment scores of surrogate signatures for TLS and IFN-gamma (IFN-γ) pathway activation were computed using the single sample gene set enrichment analysis (ssGSEA). RESULTS: PD-L1 status was 64% (21/33) concordant between the initial and recurrent lesions using a CPS 1 threshold and 67% (22/33) concordant using a CPS 20 threshold. CPS score was associated with PD-L1 gene expression levels. There was a 43% (15/35) and 66% (23/35) concordance for the IFN-γ and TLS signature scores, respectively. CONCLUSION: Our study reveals temporal heterogeneity of PD-L1 status and TLS/IFN-γ gene expression surrogates in HNSCC that need to be considered when interpreting biomarker studies.


Asunto(s)
Antígeno B7-H1 , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Antígeno B7-H1/genética , Neoplasias de Cabeza y Cuello/genética , Humanos , Recurrencia Local de Neoplasia/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Transcriptoma
7.
Radiother Oncol ; 160: 1-8, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33845043

RESUMEN

OBJECTIVE: To compare the impact of two radiation modalities on loco-regional control, survival and tumour emergence, after node dissection for an unilateral head and neck carcinoma of unknown primary (HNCUP). MATERIALS AND METHODS: This is a multicentric retrospective study of 138 patients with unilateral HNCUP treated between 2002 and 2017. The absence of primary tumour was assessed by a systematic panendoscopy and positron emission tomography. Neck dissection was initially performed for all patients. Radiation Therapy was delivered on ipsilateral lymph node areas in 62 cases (44%: UL-RT group) and on bilateral lymph node areas and the entire pharyngeal mucosa in 77 cases (56%: COMP-RT group). Impact of radiation modalities on locoregional control and overall survival was assessed using propensity score matching method in order to balance baseline characteristics between the two groups. RESULTS: The population included 80.4% men, 80.4% smokers, 32.6% P16 positive tumours and 71.0% extracapsular extension. After a median follow-up of 5 years, the locoregional control rate was 80.3% in the UL-RT group and 75.3% in the COMP-RT group (p = 0.688). The corresponding rate of contralateral lymph node recurrence was 0% versus 2.6% (p = 0.503) and the rate of tumour emergence was 11.5% versus 9.1% (p = 0.778). No significant difference was observed between the UL-RT and the COMP-RT groups for overall survival (p = 0.9516), specific survival (p = 0.4837) or tumour emergence (p = 0.9034). CONCLUSION: UL-RT seems to provide similar outcomes as COMP-RT in unilateral HNCUP post-operative management.


Asunto(s)
Carcinoma , Neoplasias de Cabeza y Cuello , Neoplasias Primarias Desconocidas , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Masculino , Recurrencia Local de Neoplasia , Puntaje de Propensión , Estudios Retrospectivos
8.
Oncotarget ; 11(18): 1618-1628, 2020 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-32405337

RESUMEN

Background: Hyperprogressive disease (HPD) rate in head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint inhibitors (ICI) was determined using tumor growth kinetics (TGK) and compared with rapidly progressive screen-failure (SF) patients. The impact of TGK on outcomes with salvage chemotherapy (SCT) was also evaluated. Results: HPD was found in 22/120 (18%) patients. Median TGK before the onset of immunotherapy (TGKpre) was 2.7 for SF patients and 4.8 for HPD patients, with no significant difference (p = 0.17). Disease control rate after initial progressive disease on ICI was 86% with SCT in case of tumor growth deceleration vs 39% in case of tumor growth acceleration. Conclusions: HPD was frequent, but TGK of HPD patients treated with ICI did not differ from SF patients, suggesting that there is no relevant causal relationship between HPD and ICI. After initial PD with ICI, tumor growth deceleration was associated with better outcomes, indicating that TGKR might be useful to detect late responders, meriting prospective investigations. Materials and Methods: TGK ratio (TGKR) was defined as the ratio of TGK on ICI (TGKpost) to TGKpre. HPD was defined as TGKR ≥ 2. TGKR >1 indicated tumor growth acceleration, while 0 < TGKR < 1 indicated tumor deceleration.

9.
Head Neck ; 42(2): 302-311, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31737971

RESUMEN

BACKGROUND: We compared the outcome of postoperative unilateral cervical nodes radiotherapy (UL-RT) vs bilateral cervical nodes plus total mucosal irradiation (COMP-RT) in the management of head and neck carcinoma of unknown primary (HNCUP). METHODS: HNCUP, defined by the absence of primary despite a PET-CT combined with a panendoscopy, were treated with curative intent by initial ipsilateral neck dissection. Sixty-nine patients with unilateral HNCUP were included: 23 received UL-RT while 46 received COMP-RT. Carcinologic outcomes and long-term quality of life (QOL) according to the QOL Questionnaire for Head and Neck 35 were assessed. RESULTS: Within 6.3 years of median follow-up, there was no significant difference in primary tumor emergence rate (P = .68), cervical node recurrence rate (P = .34), or overall survival (P = .33) between UL-RT and COMP-RT groups. A trend toward QOL improvement was observed in the UL-RT group. CONCLUSION: UL-RT seems to provide similar outcomes as COMP-RT in unilateral HNCUP management.


Asunto(s)
Carcinoma , Neoplasias de Cabeza y Cuello , Neoplasias Primarias Desconocidas , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Recurrencia Local de Neoplasia , Neoplasias Primarias Desconocidas/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Calidad de Vida , Estudios Retrospectivos
10.
Int J Pediatr Otorhinolaryngol ; 112: 121-125, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30055720

RESUMEN

Keratocystic odontogenic tumors (KCOT) are exceptional in children and adolescents as they usually occur in the third decade. The present study reports the case of a 15 years old girl who was diagnosed with a KCOT that underwent malignant transformation. KCOT diagnostic was based on clinical, radiological, histopathological and immunohistochemical findings. A conservative treatment by enucleation was performed. Histopathological analysis of the surgical specimen concluded to a KCOT, with an infra-centimetric focus of well-differentiated squamous cell carcinoma. Owing to the well-differentiated character of the squamous cell carcinoma, a single clinical and MRI surveillance every 3 months was decided, without complementary treatment.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Mandibulares/patología , Quistes Odontogénicos/patología , Tumores Odontogénicos/patología , Adolescente , Carcinoma de Células Escamosas/diagnóstico , Femenino , Humanos , Neoplasias Mandibulares/diagnóstico , Quistes Odontogénicos/diagnóstico , Tumores Odontogénicos/diagnóstico
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