Biomedical subjects

Marieta Toma

Publications and source records attributed to Marieta Toma.

3 recordsLinked to original sources

PubMed2026

Integrating NECTIN4 Amplification With Membranous Nectin-4 Expression to Develop a Scoring System for Predicting Enfortumab Vedotin Response in Urothelial Carcinoma.

PURPOSE: Enfortumab vedotin (EV) is standard therapy for metastatic urothelial carcinoma (mUC), yet the predictive relevance of NECTIN4 expression-especially membranous versus cytoplasmic-remains unclear. Here, we sought to extend previous findings on NECTIN4 gene amplification in parallel with a systematic subcellular evaluation of NECTIN4 expression. EXPERIMENTAL DESIGN: We retrospectively analyzed 179 EV-treated mUC patients. NECTIN4 amplification was assessed by FISH and NECTIN4 protein levels by IHC. A four-tier membranous scoring algorithm (0,1+,2+,3+) adapted from CAP HER2 gastric guidelines was benchmarked against H-score. We integrated amplification status with membranous staining to refine predictive stratification and compared associations with objective response rate (ORR) to EV-301 data. RESULTS: Combining membranous and cytoplasmic compartments resulted in a median composite H-score of 260 (78.2% ≥150), closely matching NECTIN4 expression prevalence reported in EV-301 (median 250; 82.6% ≥ 150). A ≥150 cut-off enriched for EV responders in both cohorts; in EV-301 with ORR of 45.8% vs. 20% (P = 0.001). High membranous expression based on the scoring (2+/3+) predicted response (ORR 55.1% vs. 25.5%; P < 0.001), with longer PFS (7.1 vs. 2.9 months; HR 0.45) and OS (12.3 vs. 6.9 months; HR 0.57), whereas cytoplasmic expression lacked predictive value. NECTIN4-amplified tumors showed particularly favorable outcomes (PFS 12.2 months; OS 30.1 months). An integrated three-tier model-amplified, non-amplified/high-membranous, and non-amplified/low-membranous-yielded ORRs of 77.2%, 42.9%, and 26.1% and separated survival outcomes. CONCLUSIONS: Our NECTIN4 scoring system integrating NECTIN4 amplification with membranous NECTIN4 expression accurately predicts outcomes, supporting combined genomic and membranous assessment as complementary biomarkers for optimizing EV selection.

Journal Article↗

PubMed2004

Immunocyt and the HA-HAase urine tests for the detection of bladder cancer: a side-by-side comparison.

OBJECTIVES: The reliable detection of bladder cancer from urine specimen remains an unsolved problem. Especially superficial bladder cancer can be missed with urine tests. We assessed the sensitivity and specificity of the commercial Immunocyt test in a side-by-side comparison with the HA-HAase urine test and cytology. The Immunocyt test measures the immunocytological expression of sulfated mucin-glycoproteins and glycosylated forms of the carcinoembryonic antigen in urine. With the HA-HAase urine test the level of hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are measured in an ELISA-like test. METHODS: A total of 94 consecutive patients were studied and among these 30 patients had bladder cancer and 64 were controls. Among bladder cancer patients, there were 14 pTa, 9 pT1, 5 pT2 and 2 carcinoma in situ (CIS) transitional cell carcinoma of the bladder, respectively. The controls consisted of 55 patients with a history of bladder cancer but no evidence of tumor at the follow-up cystoscopy and 9 benign prostatic hyperplasia (BPH) patients. The 30 transitional cell cancer specimens had 4 (13%) grade 1 tumors, 15 (50%) grade 2 tumors and 11 (37%) grade 3 tumors. Sensitivity and specificity as well as the positive and negative predictive values of each test were evaluated. RESULTS: The sensitivity of the HA-HAase urine test (83.3%; 25/30) was significantly higher than the Immunocyt at 63.3% (19/30) (p = 0.038, McNemar test) and cytology (73%; p < 0.05). The specificity of the HA-HAase test (78.1%; 50/64), Immunocyt (75%; 48/64) and cytology (79.7%; 51/64) were comparable. The prevalence of bladder cancer in our study was 31%. The positive predictive value (PPV) of the HA-HAase test (64.1%) was significantly higher than the Immunocyt test (54.3%). The negative predictive value (NPV) of the HA-HAase test (90.9%) was also higher than the Immunocyt test (81.3%). The PPV and NPV values for cytology were 62.9% and 86.4%, respectively. False negative patients in the HA-HAase urine test were 5 pTa tumors (2 G1, 2 G2 and 1 G3). False negative patients in the Immunocyt test were 7 pTa tumors (1 G1 and 6 G2), 3 pT1 (2 G2, 1 G3) and 1 pT2 G3, respectively. CONCLUSIONS: The sensitivity of the HA-HAase urine test is significantly higher than that of the Immunocyt test to detect bladder cancer. Specificity, as well as the PPV and NPV of the HA-HAase test were higher than that of the Immunocyt test. With a prevalence of 31% bladder cancer patients in all hematuria patients studied, a typical distribution of patients in a urological clinic is presented. Longer follow up of the study patients will give more information on the value of these tests in the detection of bladder cancer.

Biomarkers, Tumor↗

PubMed2002

Screening for prostate cancer in Romania.

In Romania, more than 95% of patients present with advanced stage prostate cancer at the time of diagnosis. Our purpose was to detect early prostate cancer in the Romanian city of Oradea, with a screening based on digital rectal examination and fine needle aspiration biopsy. We performed digital rectal examinations on 701 men, between 50 to 80 years of age. Four men with a history of prostate cancer were excluded from the study. Transrectal fine-needle aspiration biopsies were done in 15 men who presented with suspicious findings at the digital rectal examination. Prostate cancer was cytologically proven in eleven men. Nine of these were low- to intermediate grade (GI-II) and clinically localized (T2). Two patients had clinical stage T3 tumors. The prostate cancer detection rate in the screened population was 1.6% (11/697). Currently, eight men have undergone total retropubic prostatectomy. One patient presented with pelvic lymph node metastases and, after a staging lymphadenectomy, only a bilateral orchiectomy was performed. This first Romanian mass screening study for prostate cancer revealed a great interest in early cancer detection among the general public. Continued effort to make asymptomatic men aware of the disease may ultimately lead to an overall stage reduction at the time of diagnosis in Romania.

Aged↗