Abstract Purpose: The addition of dendritic cell vaccines (DCV) to neoadjuvant chemotherapy (NAC) could induce immune biomarker changes in those patients with residual disease (RD) by transforming tumor microenvironment. Methods: Core diagnostic biopsies and surgical specimens from 80 patients (38 in the Vaccinated Group plus NAC (VG) and 42 in the Control Group (CG) treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using Immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS III) in the core-diagnostic biopsies and in the surgical specimens, to compare the amount of TILs in each group. Results: A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). TNBC patients in the CG showed a TILs drop from 2.71% in the biopsy to 0.18% in the surgical specimen (p = 0.5). We also found that 66.7% (4/6) of TNBC patients from VG registered an increase in TILs after treatment as compared to 20% (1/5) of TNBC patients in the CG (p=0.24). This phenomenon is not observed in the other biologic subtypes. An association between before NAC CD8 TILs (4% cut-off point ) and pathological complete response in the VG was found in univariate and multivariate analysis (OR=1.41, IC95% 1.05-1.90; p=0.02, and OR=2.0, IC95% 1.05-3.9; p=0.03, respectively).Conclusion: Our findings suggest that patients with TNBC especially benefit from the stimulation of the antitumor immune system by using DCV pulsed with tumor antigens.

Tumor-infiltrating lymphocytes

Univariate analysis

10.21203/rs.3.rs-643452/v3

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Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma

Virchows Archiv (2021)

Ignacio Ruz‐Caracuel Álvaro López‐Janeiro Victoria Heredia-Soto Jorge Luis Ramon-Patino Laura Yébenes

Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours.

MSH6

10.1007/s00428-021-03176-5

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Modification of Breast Cancer Milieu with Chemotherapy plus Dendritic Cell Vaccine: An Approach to Select Best Therapeutic Strategies

Biomedicines (2023)

Luis Mejías Sosa Álvaro López‐Janeiro Alicia Córdoba Iturriagagoitia Pablo Sala Belén P. Solans

The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment.Core diagnostic biopsies and surgical specimens from 80 patients (38 in the vaccinated group plus NAC (VG) and 42 in the control group (CG, treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using immunohistochemistry and the automated cellular imaging system (ACIS III) in paired samples.A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). This enrichment was seen in up to 67% of TNBC patients in the experimental arm as compared with the CG (20%). An association between CD8 TILs before NAC (4% cut-off point) and pathological complete response in the VG was found in the univariate and multivariate analysis (OR = 1.41, IC95% 1.05-1.90; p = 0.02, and OR = 2.0, IC95% 1.05-3.9; p = 0.03, respectively).Our findings suggest that patients with TNBC could benefit from the stimulation of the antitumor immune system by using DCV together with NAC.

10.3390/biomedicines11020238

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New evidence for fibrocartilaginous dysplasia representing a variant of fibrous dysplasia

Journal of Clinical Pathology (2025)

Carlos E. de Andrea Álvaro López‐Janeiro Pancras C.W. Hogendoorn

Several types of tumours and tumour-like lesions are recognised. Their classification is based mainly on the cell or tissue differentiation pathway found within the lesion. Not all tumour cells in a bone tumour differentiate towards a single cell type. For instance, cartilage-producing cells and cartilaginous matrix are often found within osteosarcoma, and on rare occasions, cartilage can be found in fibrous dysplasia. Here, we discuss the presence of cartilaginous differentiation with fibrous dysplasia, its differential diagnosis and the use of molecular techniques to show that cartilaginous differentiation is an integral part of the lesion in that case, also known as fibrocartilaginous variant of fibrous dysplasia.

Cell type

10.1136/jcp-2024-210007

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Prognosis Stratification Tools in Early-Stage Endometrial Cancer: Could We Improve Their Accuracy?

Research Square (Research Square) (2021)

Jorge Luis Ramon-Patino Ignacio Ruz‐Caracuel Victoria Heredia-Soto L.E. García de la Calle Bulat Zagidullin

Abstract Background There are 3 prognostic stratification tools used in clinics for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address the prognosis and adjuvant therapy. Some other previously explored biomarkers have also shown prognostic relevance. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to refine the prognosis in early-stage endometrial cancer. Methods This was a retrospective single-institution cohort of patients with early-stage endometrial cancer to evaluate these stratification tools. Relapse-free survival (RFS) and overall survival of each classifier were analysed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. Results We analysed 294 patients: 88% had endometrioid histology, 69% stage Ia, and 15% had a relapse. A comparison between the 3 classifiers showed a slightly improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.79), although we did not find differences between intermediate prognostic groups. However, the inclusion of CTNNB1 status to stratify patients of intermediate groups allowed a better discrimination between the intermediate prognostic groups, resulting in a c-index of 0.82. Therefore, we propose a novel classifier based on ESGO-ESTRO-ESP 2020 and CTNNB1 , which achieved statistically significant and clinically relevant differences in 5-year RFS: 93.4% for low risk, 79.6% for intermediate merged group/ CTNNB1 wild type, and 37.3% for high risk (including patients from the merged intermediate groups with CTNNB1 mutation). Conclusions The incorporation of molecular classification in risk stratification of endometrial cancer resulted in better discriminatory capability, which was improved even further with the addition of CTNNB1 mutational evaluation.

Risk Stratification

Adjuvant Therapy

10.21203/rs.3.rs-682631/v1

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Pancreatic intraductal papillary mucinous neoplasm with sarcomatous transformation. A case report

Revista Española de Patología (2021)

Álvaro López‐Janeiro Ana Margarita Rodriguez Marta Mendiola Rula Nasimi Sabbagh J A Sampedro Feliu

Neoplasm

Malignant Transformation

10.1016/j.patol.2021.05.004

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