Investigator

Antonio Travaglino

Associate Professor of Pathology · University of Insubria, Department of Medicine and Technological Innovation

ATAntonio Travaglino
Papers(12)
Immunophenotype of ut…Endometrial stromal t…Impact of optimal sec…Race and ethnicity re…Predictive factors of…Histological Prognost…Predictive Accuracy o…Diagnostic Pitfalls R…Clinical features of …Metabolomics in endom…Histopathological cha…Predictive accuracy o…
Collaborators(10)
Antonio RaffoneDiego RaimondoFrancesco FanfaniFrediano InzaniGabriele SacconeGian Franco ZannoniGiovanni ScambiaGiulia PellecchiaDamiano ArciuoloLorenza Driul
Institutions(7)
University Of InsubriaUniversity of Naples …IRCCS Azienda Ospedal…Università Cattolica …Università degli Stud…University Of PisaUniversity of Udine

Papers

Immunophenotype of uterine tumor resembling ovarian sex cord tumor (UTROSCT): Case series and meta-analysis of the literature

This study aimed to define the frequency of positivity of several immunohistochemical markers in uterine tumor resembling ovarian sex cord tumor (UTROSCT). All consecutive UTROSCT cases were retrieved from consultation files of one of the authors. Histological and immunohistochemical slides were reviewed. In addition, three electronic databases were searched from their inception to January 2024 for all studies assessing the immunophenotype of UTROSCT. Exclusion criteria were: sample size < 10 patients, overlapping patient data, reviews. Endometrial stromal tumors with sex cord-like areas (formerly called "type I UTROSCT") were excluded. Immunohistochemical markers assessed in ≥ 10 cases in at least 3 different series were included. For each marker, pooled positivity rate was calculated by using a random effect model; mean labeling index was calculated for Ki67. Thirty UTROSCT cases were retrieved Six studies were included, and 30 new cases were obtained, with a total of 181 UTROSCTs. Fourteen immunohistochemical markers were assessed. Pooled positivity rates were (in descending order): CD56 = 97 %, progesterone receptor = 91 %, estrogen receptor = 85.5 %, WT1 = 84 %, wide-spectrum cytokeratins = 78.7 %, CD99 = 77 %, desmin = 74.5 %, calretinin = 70.6 %, smooth muscle actin = 56.4 %, inhibin = 44.5 %, CD10 = 41 %, caldesmon = 21.9 %, Melan-A/MART-1 = 10.4 %. Mean Ki67 labeling index was 8.7 %. Immunophenotypically, UTROSCT is less consistent than ovarian sex cord tumors and overlaps with other mesenchymal and epithelial tumors; an integrated clinico-pathological and immunohistochemical evaluation appears necessary for a correct diagnosis.

Impact of optimal secondary cytoreductive surgery on survival outcomes in women with recurrent endometrial carcinoma: A systematic review and meta‐analysis

AbstractBackgroundManagement of recurrent endometrial carcinoma (EC) represents a challenge. Although a complete resection of visible disease at secondary surgery (R0) is recommended, the impact of R0 on survival outcomes is unclear and pooled data are lacking.ObjectiveTo quantitatively assess the impact of R0 on survival outcomes in women with EC recurrence.Search StrategyA systematic review and meta‐analysis was performed searching eight electronic databases from their inception up to January 2024.Selection CriteriaAll peer‐reviewed studies that assessed quantitatively the impact of R0 on survival outcomes in women at first EC recurrence were included.Data Collection and AnalysisHazard ratio (HR) with 95% confidence interval (CI) for death of any cause and secondary recurrent or progressive disease in women with EC recurrence who underwent R0 compared to non‐optimal secondary surgical cytoreduction (R1) were pooled and assessed at both univariable and multivariable analyses.Main ResultsThree studies with 442 patients were included. At univariate analysis, in women with EC recurrence and R0 compared to women with EC recurrence and R1, pooled HR was 0.451 (95% CI: 0.319–0.638) for death from any cause, and 0.517 (95% CI: 0.298–0.895; p = 0.019) for recurrent or progressive disease.At multivariate analysis, in women with EC recurrence and R0 compared to women with EC recurrence and R1, pooled HR was 0.447 (95% CI: 0.255–0.783; p = 0.005) for death from any cause, and 0.585 (95% CI: 0.359–0.952; p = 0.031) for recurrent or progressive disease.ConclusionIn women with EC recurrence, R0 is an independent prognostic factor, decreasing the risk of death from any cause by approximatively 55%, and of recurrent or progressive disease by approximatively 40%, compared to R1.

Race and ethnicity reporting in endometrial cancer literature

There is evidence that there are differences in survival outcomes among patients with endometrial cancer of different ethnic groups. We aimed to assess the quantity and quality of race/ethnicity reporting in the literature on endometrial cancer published from January 2020 to December 2020. In this systematic review, electronic searches of PubMed, MEDLINE, Web of Sciences, Scopus, and Cochrane Library databases were performed for all articles published in 2020. A total of 3330 articles were reviewed, of which 949 (35%) peer-reviewed human-based articles focusing on endometrial cancer were included. Non-research-focused articles, review articles, meta-analyses, case reports, and non-human studies were excluded. We analyzed the proportion of studies reporting race/ethnicity and assessed the quality of reporting with regard to the adherence to the International Committee of Medical Journal Editors (ICMJE) recommendations. We evaluated the influence of study characteristics on race/ethnicity reporting and compared articles published in journals which adhere to the ICMJE recommendations against those that did not explicitly state that they did. Of the 949 (28.5%) included articles, 166 (17.5%) reported race/ethnicity of patients, with low quality of reporting. The reporting rate of race/ethnicity was similar when comparing articles from ICMJE and non-ICMJE journals (62 (20.4%) vs 104 (16.1%); p=0.11), prospective versus retrospective studies (53 (22.7%) vs 113 (15.8%); p=0.02), and national versus international studies (147 (17.5%) vs 19 (17.4%); p=0.99). Studies performed in the WHO region of Americas were significantly more consistent in reporting race compared with other regions (119 (44.7%) vs 23 (6.8%) European, 2 (7.4%) Eastern Mediterranean, 21 (7.1%) Western Pacific, 0 (0%) South-East Asia; p<0.001). Female corresponding authors were significantly more consistent in reporting race than male authors (94 (22.5%) vs 72 (13.6%); p<0.001). Human-based articles focusing on endometrial cancer have a low frequency and quality of race/ethnicity reporting, even in journals claiming to follow ICMJE recommendations.

Histological Prognostic Factors of Endometrial Cancer in Patients with Adenomyosis: A Systematic Review and Meta-Analysis

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological prognostic factors. However, pooled risk of EC unfavorable histological prognostic factors in patients with adenomyosis has never been calculated. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; We aimed to assess the risk of EC unfavorable histological prognostic factors in patients with adenomyosis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; All studies with data about histological prognostic factors of EC in patients with and without adenomyosis were included. Relative risk for each unfavorable histological prognostic factor of EC, such as nonendometrioid histotype, FIGO grade 3, FIGO stage II–IV, lymphovascular space invasion (LVSI), and deep myometrial invasion, was calculated in patients with adenomyosis compared to patients without adenomyosis. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Seven studies with 4,439 patients were included in the quantitative analysis. EC patients with adenomyosis showed a pooled RR of 0.77 (&lt;i&gt;p&lt;/i&gt; = 0.05) for nonendometrioid histotype, 0.55 (&lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.00001) for FIGO grade 3, 0.60 (&lt;i&gt;p&lt;/i&gt; = 0.005) for FIGO stage II–IV, 0.75 (&lt;i&gt;p&lt;/i&gt; = 0.004) for LVSI, and 0.65 (&lt;i&gt;p&lt;/i&gt; = 0.001) for deep myometrial invasion. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; EC patients with adenomyosis have a significantly decreased risk for unfavorable histological prognostic factors of EC compared to EC patients without adenomyosis. Such findings might explain the supposed better EC prognosis in patients with adenomyosis.

Predictive Accuracy of Progesterone Receptor B in Young Women with Atypical Endometrial Hyperplasia and Early Endometrial Cancer Treated with Hysteroscopic Resection plus LNG-IUD Insertion

The immunohistochemical expression of isoform B of the progesterone receptor (PRB) has shown promising results in predicting the response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. We aimed to calculate the accuracy of PRB as a predictive marker of conservative treatment outcome in AEH or EEC. Retrospective cohort study. University of Naples Federico II, Naples, Italy. Thirty-six consecutive premenopausal women <45 years of age with AEH (n = 29) or EEC (n = 7) conservatively treated from January 2007 to June 2018 were retrospectively assessed. All patients had been treated with hysteroscopic resection plus levonorgestrel-releasing intrauterine device insertion and followed for at least 1 year. The immunohistochemical expression of PRB was separately assessed in the glands and stroma of the lesion and dichotomized as "weak" or "normal." The treatment outcomes considered were (1) treatment failure (i.e., a combined outcome including no regression or recurrence); (2) no regression; and (3) recurrence. The predictive accuracy of PRB immunohistochemistry was assessed by calculating sensitivity (SE), specificity (SP), and area under the receiver operating characteristic curve (AUC). A weak glandular PRB expression showed SE = 70%, SP = 77%, and AUC = 0.74 for treatment failure; SE = 66.7%, SP = 70%, and AUC = 0.68 for no regression; and SE = 75%, SP = 68.8%, and AUC = 0.72 for recurrence. A weak stromal PRB expression showed SE = 100%, SP = 53.8%, and AUC = 0.77 for treatment failure; SE = 100%, SP = 46.7%, and AUC = 0.73 for no regression; and SE = 100%, SP = 43.8%, and AUC = 0.72 for recurrence. A weak stromal PRB expression is a highly sensitive predictive marker of both no response and recurrence of AEH and EEC conservatively treated.

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Abstract Background The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking. Objective To provide a clinical characterization of the ProMisE groups of EC. Methods A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated. Results Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%. Conclusion The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.

Histopathological characterization of ProMisE molecular groups of endometrial cancer

After the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) development, endometrial cancer (EC) may be reclassified in four novel prognostic groups: POLE-mutated (POLE-mt), mismatch-repair-deficient (MMR-d), p53-abnormal (p53abn), p53-wild-type (p53wt). However, histopathological characteristics of each ProMisE group are still undefined. Such characterization may be useful to understand how this novel molecular classifier may change the current patient management, reducing over- and undertreatment. To provide a histopathological characterization of ProMisE groups of EC, in terms of histological grade (G3 vs G1-2), histotype, lymphovascular space invasion (LVSI), deep myometrial invasion (>50%), lymph node involvement, and European Society for Medical Oncology (ESMO) risk category. A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to May 2019, for studies that reported histopathological characteristics of each ProMisE group. Pooled prevalence of each histopathological characteristic of EC in each ProMisE group was calculated. Four studies with 1171 patients were included in the systematic review, out of which three studies with 912 patients were included in the meta-analysis. Pooled prevalence estimates were: CONCLUSIONS: The histopathological characterization of the ProMisE groups suggests that many patients are currently undertreated or overtreated (especially in the POLE-mt and MMR-d groups).

Gardnerella vaginalis and Trichomonas vaginalis infections and the risk of persistence or progression of low-grade cervical intraepithelial neoplasia

Gardnerella vaginalis (GV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for persistence or progression of low-grade precancerous cervical lesions (CIN1/L-SIL). However, their role is still undefined. We aimed to assess if GV and TV infections affect the risk of persistence/progression of CIN1/L-SIL. A retrospective cohort study was performed to assess the risk of CIN1/L-SIL persistence or progression, persistence alone and progression alone in patients with GV and/or TV infections (GV + and/or TV+), only GV (GV+), only TV (TV+), or GV and TV coinfections compared to patients without these infections. Relative risk (RR) with 95 % confidence intervals (CI) was adopted (significant p-value>0.05). Two hundred and seventy patients were included. RR for CIN1/L-SIL persistence or progression was 1.63 in GV + and/or TV+ (p = 0.02), 1.99 in GV+ (p = 0.0008), 0.25 in TV+ (p = 0.32), 1.78 in coinfection (p = 0.26). RR for persistence was 1.55 in GV + and/or TV+ (p = 0.1), 2.179 in GV+ (p = 0.0013), 0.32 in TV+ (p = 0.41), 0.45 in coinfection (p = 0.55). RR for progression was 1.92 in GV + and/or TV+ (p = 0.22), 1.34 in GV+ (p = 0.68), 1.16 in TV+ (p = 0.91), 8.39 in coinfection (p = 0.0002). In conclusion, GV infection may be a risk factor for CIN1/L-SIL persistence. TV infection alone does not significantly affect the risk of persistence or progression of such lesions, while it may greatly increase the risk of progression when associated with GV infection.

BAG3 expression correlates with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix

AbstractIntroductionBcl‐2‐associated athanogene 3 (BAG3) is a protein involved in apoptosis and stress response, which is overexpressed in invasive cervical cancer. However, nothing is known about BAG3 expression in precancerous lesions of the uterine cervix. We aimed to evaluate the expression of BAG3 in cervical intraepithelial neoplasia/squamous intraepithelial lesions (CIN/SIL).Material and methodsForty patients (16 CIN1/L‐SIL, 11 CIN2/H‐SIL and 13 CIN3/H‐SIL) were assessed by immunohistochemistry for BAG3. The intensity of BAG3 expression was categorized as null, minimal, weak, moderate or strong. The association of BAG2 intensity of expression with the grade of dysplasia was assessed using Chi‐square test (significant P value &lt;0.05).ResultsIn all normal controls, BAG3 expression was negative. In L‐SIL specimens, BAG3 expression was confined to the basal third of the epithelium, with an intensity minimal in nine cases (56.3%), weak in six (37.5%) and strong in one (6.3%). In H‐SIL specimens, BAG3 expression involved also the two upper thirds of the epithelium, with an intensity moderate in 13 cases (54.2%; 8 CIN2 and 5 CIN3) and strong in 11 cases (45.8%; 3 CIN2 and 8 CIN3). The distribution of BAG3 expression correlated perfectly with the grade of dysplasia (P = 0.0); a moderate/strong expression of BAG3 was significantly associated with H‐SIL (P &lt; 0.0001), with no significant difference between CIN2 and CIN3 (P = 0.1228).ConclusionsIn CIN/SIL, both distribution and intensity of BAG3 expression correlate directly with the grade of dysplasia, supporting the involvement of BAG3 in all phases of cervical carcinogenesis and its possible diagnostic and prognostic role in cervical premalignant lesions.

Gardnerella vaginalis and Trichomonas vaginalis infections as risk factors for persistence and progression of low-grade precancerous cervical lesions in HIV-1 positive women

Gardnerella vaginalis (GV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for persistence and/or progression of low-grade cervical precancerous lesions (CIN1/L-SIL). In patients with Human Immunodeficiency Virus (HIV), who have an increased baseline risk of CIN1/L-SIL progression, the role of GV and TV is undefined. We aimed to investigate the prognostic impact of GV and TV infections on CIN1/L-SIL in HIV-positive women. HIV-1-positive women with L-SIL were retrospectively included. The risk of persistence or progression in the case of any infection (primary outcome), only GV (GV+), only TV (TV+), or GV and TV coinfection (secondary outcomes) was calculated compared to women with no GV or TV infections (NI), by using relative risk (RR) and multivariate logistic regression, with a significant p-value>0.05;. One hundred and ninety-two patients were included (18.2 %GV+, 15.6 %TV+, 5.2 % coinfection, 60.9 %NI); 58 CIN1/L-SIL showed persistence and 46 progression. RR for persistence/progression of CIN1/L-SIL in the case of any infection was 1.56 (1.21-2.01; p = 0.0006) compared to NI. RR for persistence alone was 1.91 (1.25-2.09; p = 0.0026) in GV+, 1.2 (0.63-2.3; p = 0.5736) in TV+, and 2.06 (1.09-3.9; p = 0.0254) in coinfection. RR for progression alone was 1.94 (1.06-3.4; p = 0.0311) in GV+, 2.14 (1.25-3.67; p = 0.0058) in TV+, and 2.73 (1.39-5.37; p = 0.0036) in coinfection. On multivariate analysis, the presence of any infection was significantly associated with persistence/progression (p = 0.002), GV + with persistence (p = 0.019) and TV + with progression (p = 0.016). In conclusion, GV infection is a risk factor for persistence of CIN1/L-SIL in HIV-positive women, while TV infection is a risk factor for progression. Women with these infections may require a closer and more careful follow-up of CIN1/L-SIL.

120Works
20Papers
18Collaborators
Endometrial NeoplasmsBiomarkers, TumorPrognosisPrecancerous ConditionsDiagnosis, DifferentialNeoplasm ProteinsApoptosis Regulatory ProteinsUterine Cervical Neoplasms

Positions

2023–

Associate Professor of Pathology

University of Insubria · Department of Medicine and Technological Innovation

2023–

Pathologist

Casa di Cura Malzoni - Villa Platani

2021–

Pathologist

Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Depatment of Woman and Child's Health Sciences

Education

2023

PhD program in biomorphological and surgical sciences

University of Naples Federico II · Department of Advanced Biomedical Sciences

2020

Pathology Residency Program

University of Naples Federico II · Department of Advanced Biomedical Sciences

2016

Degree course in medicine and surgery

University of Naples Federico II

Country

IT