Papers by Valerio Gaetano Vellone
Frontiers in Immunology, Aug 22, 2023
Background: we evaluated the concordance between immunohistochemical p53 staining and TP53 mutati... more Background: we evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups. Methods: patients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS). Results: 34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16]. Conclusion: immunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup.
Ultrasound in Obstetrics & Gynecology, Oct 1, 2020
Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional. Salud Pub... more Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional. Salud Publica Mex 2012;54:418-424. Resumen Objetivo. Los donadores de metilo como el ácido fólico previenen defectos del tubo neural (DTN), pero estudios recientes sugieren que también favorecen el desarrollo de asma. En este trabajo exploramos una posible asociación ecológica entre DTN y asma. Material y métodos. Se consultaron bases de datos de México y EUA para obtener información sobre distribución geográfica (por estado) y tendencia temporal (por año) de DTN y asma. Resultados. Los estados con menor frecuencia de DTN tuvieron mayor frecuencia de asma, tanto en México (r S =-0.48, p=0.005) como en EUA (r S =-0.39, p=0.005). Las tendencias temporales también mostraron correlación inversa en México (1997-2007, r S =-0.73, p=0.01) y EUA (1979-1998, r S =-0.91, p<0.001). Conclusiones. En ambos países la frecuencia de asma correlacionó de forma inversa con la frecuencia de DTN, tanto en distribución geográfica como en tendencias anuales, apoyando la posibilidad de que la ingestión de donadores de metilo en la dieta o como suplementos esté influyendo sobre la frecuencia de asma. Palabras clave: asma; defectos del tubo neural; anencefalia; espina bífida; epigenómica; estudios ecológicos; ácido fólico Vargas MH, Campos-Bedolla P, Segura P. Inverse association between asthma and neural tube defects: a binational ecological study.
Ultrasound in Obstetrics & Gynecology, Oct 1, 2020
medRxiv (Cold Spring Harbor Laboratory), Dec 11, 2020
Ultrasound in Obstetrics & Gynecology, Sep 1, 2017
Oral communication abstracts intestinal lesions was associated with increased stool frequency and... more Oral communication abstracts intestinal lesions was associated with increased stool frequency and softer stools; and pouch of Douglas obliteration was associated with a residual feeling after defecation. A higher score on the gastrointestinal symptom questionnaire was associated with pouch of Douglas obliteration and uterosacral ligament involvement on TVUS (all p<0.05). Conclusions: We observed a high prevalence of GIC in women referred to an endometriosis clinic. The presence of GIC should prompt an earlier evaluation for endometriotic lesions, which may potentially reduce the delay in diagnosis in these patients. OC22.04 Transvaginal ultrasonography combined with computed tomographic colonography in the diagnosis of bowel endometriosis
Ultrasound in Obstetrics & Gynecology, Apr 1, 2017
Objective To compare the accuracy of magnetic resonance enema (MR-e) and rectal water-contrast tr... more Objective To compare the accuracy of magnetic resonance enema (MR-e) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis. Methods This prospective study included 286 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent MR-e and RWC-TVS before laparoscopic excision of endometriotic lesions. The findings of MR-e and RWC-TVS were compared with surgical and histological results.
Pathologica, 2013
Chemo-radiation represents an effective therapy for carcinoma of the uterine cervix. The endometr... more Chemo-radiation represents an effective therapy for carcinoma of the uterine cervix. The endometrium may however receive a consistent dose of mutagenic radiations and patients may have an increased risk of secondary malignancies. Endometrial mixed malignant mullerian tumor (MMMT) is a rare, highly aggressive disease, and neuroendocrine features are even rarer. A 68 years old woman underwent radio-chemotherapy for a squamous cell carcinoma of the cervix. Follow up was uneventful until, eight years after radio-chemotherapy, imaging exams detected a diffuse enlargement of the uterine body. Radical hysterectomy revealed a multiphasic lesion with both sarcomatous and mixed carcinomatous components. The carcinomatous, component presented neuroendocrine histologic and ultrastuctural features and an intense expression of neuroendocrine immunohistochemistry markers. No residual cervical carcinoma was documented (pR0). The patient died of disease after 9 months. Reported cases further demonstrate how the irradiation of the uterus for cervical cancer carries a not negligible risk of developing a second endometrial cancer. The second cancer may develop years after initial therapy and may have aggressive histologic and clinical features. This case underlines the importance for a long follow-up in women having received radio-chemotherapy alone.
Ultrasound in Obstetrics & Gynecology, Apr 1, 2017
Objectives To compare the performance of computed tomographic colonography (CTC) and rectal water... more Objectives To compare the performance of computed tomographic colonography (CTC) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis, and compare precision in estimating the length of the rectosigmoid nodules and the distance between the nodules and the anal verge. Methods This prospective study included 70 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent RWC-TVS and CTC before laparoscopic excision of endometriotic nodules. The findings of RWC-TVS and CTC were compared with surgical and histological results. Results Of the 70 patients included in the study, 40 (57.1%) had rectosigmoid endometriosis. CTC and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.508) and similar precision in estimating the length of the endometriotic nodules (P = 0.077). CTC was more precise than RWC-TVS in estimating the distance between the rectosigmoid nodule and the anal verge (P < 0.001). The intensity of pain experienced during CTC was higher than that perceived during RWC-TVS (P < 0.001); however, intestinal distension for CTC was well-tolerated in all patients without significant adverse effects. Conclusions RWC-TVS and CTC have similar accuracy in the diagnosis of rectosigmoid endometriosis and similar precision in estimating the size of the nodules; however, CTC is more precise than RWC-TVS in estimating the
Expert Opinion on Pharmacotherapy, Sep 7, 2015
Endometriosis is an estrogen-dependent chronic disease requiring long-term therapy. Therefore, th... more Endometriosis is an estrogen-dependent chronic disease requiring long-term therapy. Therefore, the choice of medical treatment should be based on efficacy, preference of patients, incidence and severity of adverse effects and cost. This review briefly summarizes the currently available medical treatment for endometriosis. The treatments most recently proposed for endometriosis will be described in detail, including gonadotropin-releasing hormone (GnRH) antagonists, aromatase inhibitors (AIs) and the flexible extended combined oral contraceptive. The oral contraceptive pill and progestogens allow for the treatment of the majority of patients with endometriosis. The flexible extended dosing regimen, containing drospirenone and ethinylestradiol, may be particularly useful in patients suffering severe dysmenorrhea and improving the adherence and compliance with treatment. GnRH agonists may be used in patients resistant to first-line therapy; up to now, limited data are available on the use of GnRH antagonist (such as elagolix) in patients with endometriosis. AIs should be regarded as experimental therapies and used only in patients with symptoms resistant to other therapies; however, the use of these drugs is limited by the possibility to administer the treatment for short-term periods only (6 months) and, similarly to GnRH antagonists, by the high incidence of adverse effects, requiring the use of add-back therapy.
Pathologica, Apr 1, 2022
Microcystic/reticular (MRV) schwannoma has been described since 2008, but remains a rarely encoun... more Microcystic/reticular (MRV) schwannoma has been described since 2008, but remains a rarely encountered entity. MRV has a predilection for visceral locations and has variable histologic appareances. Given its rarity and anatomic variability, this entity could raise differential diagnostic issues with other tumours and malignancies. We describe the case of a 69-year-old male followed at IRCCS Ospedale Policlinico San Martino of Genoa for his previous history of non-Hodgkin lymphoma. A para-aortic mass was discovered during follow-up, which-due to its stability, also after chemotherapy-had been hypothesized to be a non-lymphomatous lesion; given the dimensions and the site, the mass was removed. Histological evaluation showed a nodule limited by a slight fibrous capsule and characterized by a proliferation of medium-sized fusiform cells, with elongated nuclei and scarce eosinophilic cytoplasm. Given the lack of malignant signs and the strong expression of protein S-100, a diagnosis of mesenchymal neoplasia with expression of neural markers compatible with reticular schwannoma was made. The neoplasm has not recurred since its removal. The case we present is, at our best knowledge, the first described in the retroperitoneum, a site where the exclusion of other mesenchymal malignancies is mandatory. The rarity and variability of presentations could create problems of differential diagnosis both with mucinous-producing carcinomas or with other soft tissue tumours, with myxoid or reticular structure. The description of this case could help raise information on this rare neoplasm and help distinguish it from other malignancies, especially in unusual sites.
Annals of Translational Medicine, Dec 1, 2019
British Journal of Cancer, Apr 19, 2023
BACKGROUND: The distribution of ovarian tumour characteristics differs between germline BRCA1 and... more BACKGROUND: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. METHODS: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). RESULTS: No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. CONCLUSIONS: We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.
Cancers
Background: Prognostic and predictive factors for patients with metastatic renal cell carcinoma (... more Background: Prognostic and predictive factors for patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy are highly warranted, and the immune tumor microenvironment (I-TME) is under investigation. Methods: The Meet-URO 18 was a multicentric retrospective study assessing the I-TME in mRCC patients treated with ≥2nd-line nivolumab, dichotomized into responders and non-responders according to progression-free survival (≥12 months and ≤3 months, respectively). The primary objective was to identify differential immunohistochemical (IHC) patterns between the two groups. Lymphocyte infiltration and the expressions of different proteins on tumor cells (CD56, CD15, CD68, and ph-mTOR) were analyzed. The expression of PD-L1 was also assessed. Results: A total of 116 tumor tissue samples from 84 patients (59% were primary tumors and 41% were metastases) were evaluated. Samples from responders (N = 55) were significantly associated with lower expression of CD4+ T lymphoc...
Journal of Clinical Pathology
AimsAccording to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abn... more AimsAccording to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1).Methods117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotype...
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Papers by Valerio Gaetano Vellone