TP53 mutations and survival in patients with histologically defined Glioblastoma, IDH-wildtype.

BACKGROUND: Mutations of the TP53 oncosuppressor gene are frequent events in patients with malignant tumors including IDH-wildtype GBM (GBM IDH wt). However, the effective impact of TP53 mutations on prognosis has been poorly evaluated. METHODS: We performed a retrospective study investigating the impact of TP53 mutations on patients with GBM IDH wt. Only patients with PS=0-1, treated with temozolomide concurrent with and adjuvant to radiotherapy, and younger than 70 years assessed with NGS were included in the analysis. RESULTS: 97 GBM IDH wt have been selected. The median follow-up was 34.5 months (95 %CI, 30.6 - NA). Overall, 20 patients (19.4 %) presented a TP53 mutation. There were no significant differences in terms of TERT mutation (75 % vs 79.2 %) between TP53 mutated and TP53 wild-type (wt) patients. We detected 6 TP53 mutations not previously described within GBM IDH wt patients. The overall survival (OS) did not significantly differ between TP53 mutated and wt patients (HR 0.69, 95 %CI 0.37-1.27, p = 0.24). Considering only patients with an OS longer than 36 months (n = 10), the presence of a TP53 mutation was significantly associated with prolonged survival (45.6 months vs Not Reached, p = 0.037). CONCLUSION: The presence of a TP53 mutation does not appear to be correlated with overall survival in this patient cohort. While there is an association with survival for patients with an OS of 36 months or longer, the number of patients is low and there is no available evidence correlating TP53 mutations to long-term survivors.

Direct healthcare costs of oral cancer: A retrospective study from a tertiary care center.

The aim of this study was to retrospectively evaluate the direct costs of OSCC treatment and postsurgical surveillance in a tertiary hospital in northeast Italy. Sixty-three consecutive patients surgically treated for primitive OSCC at S. Orsola Hospital in Bologna (Italy) between January 2018 and January 2020 were analyzed. Billing records of the Emilia Romagna healthcare system and institutional costs were used to derive specific costs for the following clinical categories: operating theatre costs, intensive and ordinary hospitalization, radiotherapy, chemotherapy, postsurgical complications, visits, and examinations during the follow-up period. The study population comprised 17 OSCC patients classified at stage I, 14 at stage II, eight at stage III, and 24 at stage IV. The estimated mean total direct cost for OSCC treatment and postsurgical surveillance was €26 338.48 per patient (stage I: €10 733, stage II: €19 642.9, stage III: €30 361.4, stage IV: €39 957.2). An advanced diagnosis (stages III and IV), complex surgical procedure, and loco-regional recurrences resulted in variables that were significantly associated with a higher cost of OSCC treatment and postsurgical surveillance. Redirection of funds used for OSCC treatment to screening measures may be an effective strategy to improve overall health outcomes and optimize national health resources.

Thirteen-gene DNA methylation analysis of oral brushing samples: A potential surveillance tool for periodic monitoring of treated patients with oral cancer.

BACKGROUND: We evaluated the prognostic role of 13-gene DNA methylation analysis by oral brushing repeatedly performed during the follow-up of patients surgically treated for oral cancer. METHODS: This is a nested case-control study including 61 patients for a total of 64 outcomes (2/61 patients experienced multiple relapses). Samples were collected at baseline (4-10 months after OSCC resection) and repeatedly every 4-10 months until relapse or death. DNA methylation scores were classified as persistently positive, persistently negative, or mixed. RESULTS: Twenty cases who had persistently positive scores and 30 cases with mixed scores had, respectively, an almost 42-fold (p < 0.001) and 32-fold (p = 0.006) higher likelihood of relapse, compared to 14 patients with persistently negative scores. The last score before reoccurrence was positive in 18/19 secondary events. CONCLUSIONS: The 13-gene DNA methylation analysis may be considered for the surveillance of patients treated for oral carcinoma.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardized reporting systems for nongynecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung, and more. In February 2018, the first edition Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of Non-Neoplastic, benign, and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, and updates in nomenclature. CONCISE SENTENCE: The second edition of the Milan System for Reporting Salivary Gland Cytopathology, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, updates in nomenclature, and a guide to the practical application of the latest ancillary markers for the diagnosis of selected salivary gland fine-needle aspiration cases.

Pre-operative incisional biopsy of oral squamous cell carcinoma: high podoplanin expression is related to perineural invasion and may be a useful predictor of disease progression.

OBJECTIVE: Immunohistochemical analysis of podoplanin expression as a pre-operative molecular marker for perineural invasion (PNI) may represent an attractive strategy for surgical management of oral squamous cell cancer (OSCC). We evaluated the relationship between podoplanin expression and PNI in pre-operative incisional biopsies of OSCC. STUDY DESIGN: After performing pathological staging and histologic and immunohistochemical evaluation of 83 surgical specimens, we performed multivariable logistic regression analysis to examine the relationship between PNI and independent variables. To evaluate the utility of podoplanin immunopositivity for discrimination of PNI status pre-operatively, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value. We performed receiver operating characteristic curve analysis to evaluate the diagnostic accuracy of podoplanin immunopositivity for predicting PNI alone and in combination with age, T stage, N stage, and index site. RESULTS: We observed podoplanin expression in 42 (50.6%) of all the 83 pre-operative incisional biopsies and 29 of the pre-operative biopsies of the 31 (93.5%) postoperative specimens with PNI. The rate of podoplanin expression was significantly higher in patients with pT3 to pT4 stage and pN+ stage disease. Podoplanin positivity in the pre-operative biopsy showed high sensitivity in predicting PNI in the surgical specimen. CONCLUSION: Podoplanin expression appears to be an independent pre-operative variable significantly related to PNI and a possibly valuable prognostic marker for therapeutical planning and surgical treatment of OSCC.