Improving diagnostic strategies for ovarian cancer in Filipino women using ultrasound imaging and a multivariate index assay.

OBJECTIVE: To evaluate the clinical performance and overall utility of imaging and biomarker assays in discriminating between benign and malignant ovarian masses in a Filipino population. METHODS: This is a prospective cohort study among Filipino women undergoing assessment for an ovarian mass in a tertiary center. All included patients underwent a physical examination before level III specialist ultrasonographic and Doppler evaluation, multivariate index assay (MIA2G), and surgery for an adnexal mass. Ovarian tumors were classified as high-risk for malignancy based on the International Ovarian Tumour Analysis (IOTA) - Logistic Regression 2 (LR2) score. The ovarian imaging and biomarker results were correlated with the reference standard: histological findings. RESULTS: Among the 379 women with adnexal masses enrolled in this study, 291 were evaluable with ultrasound imaging, biomarker assays, and histopathological results. The risk of malignancy was higher for women classified as high-risk based on IOTA-LR2 (≥10%). The sensitivity, specificity, and diagnostic accuracy for the prediction of malignancy were 81.2%, 81%, and 0.81 (95% CI: 0.77-0.86) for IOTA-LR2; 77.5%, 66.7%, and 0.72 (95% CI: 0.67-0.77) for CA-125; and 91.3%, 41.2%, and 0.66 (95% CI: 0.62-0.71) for MIA2G. A combination of IOTA-LR2 and MIA2G significantly influenced the diagnostic performance and the result. When MIA2G was combined with IOTA-LR2 in parallel, the sensitivity (94.2%) and NPV (87.7%) increased, but the specificity (37.3%) decreased. When combined with IOTA-LR2 in series, there were fewer false positives, which resulted in improved specificity (85%). CONCLUSION: This study determined the utility of ovarian imaging and a second-generation multivariate index assay in predicting the risk of ovarian malignancy. IOTA-LR2 and MIA2G were useful in classifying patients with a high risk for ovarian malignancy.

Clinical Performance of a Multivariate Index Assay in Detecting Early-Stage Ovarian Cancer in Filipino Women.

This study evaluated the clinical performance and overall utility of a multivariate index assay in detecting early-stage ovarian cancer in a Filipino population. This is a prospective cohort study among Filipino women undergoing assessment for an ovarian mass in a tertiary center. Patients diagnosed with early-stage ovarian cancer and who underwent a physical examination before level III specialist ultrasonographic and Doppler evaluation, multivariate index assay (MIA2G), and surgery for an adnexal mass were included in this study. Ovarian tumors were classified as high-risk for malignancy based on the IOTA-LR2 score. The ovarian imaging and biomarker results were correlated with the reference standard: surgico-pathologic findings. The MIA2G exhibited the best overall performance among individual classifiers with a sensitivity of 91.7% and NPV of 84.7%, with a concomitant higher sensitivity in early-stage disease, whether as an individual classifier (93.5%) or in serial combination with ultrasound (85.5%). The performance of biomarkers (specificity, positive predictive values, and AUROC) such as MIA2G and CA-125 significantly improved when combined with an ultrasound risk scoring approach (p < 0.01). MIA2G showed a higher sensitivity for detecting lesions among EOC and late-stage ovarian cancers than otherwise. The application of biomarkers for evaluating ovarian masses in our local setting is secondary to ultrasound but adopting multivariate index assays rather than CA-125 would increase the detection of early-stage ovarian cancers regardless of menopausal status. This is most relevant in areas where level III sonographers or gynecologic oncologists are limited and preoperative referrals to these specialists can improve the survival of our patients.

Atypical lipomatous tumor of the oropharynx: A case report.

Atypical lipomatous tumor or well-differentiated liposarcoma is a rare condition in the laryngopharynx. We present a case of a 63 year-old male with progressive dysphagia who later manifested with a mass that regurgitates outside the oral cavity. Surgical removal was done via a transoral approach, followed by adjuvant radiotherapy.

Diagnostic Performances of Ultrasound-Based Models for Predicting Malignancy in Patients with Adnexal Masses.

This study compared the diagnostic performance of different ultrasound-based models in discriminating between benign and malignant ovarian masses in a Filipino population. This was a prospective cohort study in women with findings of an ovarian mass on ultrasound. All included patients underwent a physical examination before level III specialist ultrasonographic and Doppler evaluation using the different International Ovarian Tumor Analysis (IOTA) Group's risk models. Serum CA-125 and a second-generation multivariate index assay (MIA2G) were also determined for all patients. The ovarian imaging and biomarker results were correlated with the histological findings. A total of 260 patients with completed ultrasound, CA-125, MIA2G, and histopathologic results was included in the study. The presence of papillae with blood flow and irregular cyst walls during the ultrasound were significantly associated with a 20-fold (OR: 20.13, CI: 8.69−46.67, p < 0.01) and 10-fold (OR: 10.11, CI: 5.30−19.28, p < 0.01) increase in the likelihood of a malignant lesion, respectively. All individual sonologic procedures performed well in discerning malignant and benign ovarian lesions. IOTA-LR1 showed the highest accuracy (82.6%, 95% CI: 77.5−87%) for identifying ovarian cancer. IOTA-ADNEX showed the highest sensitivity (93.3%, 95% CI: 87.2−97.1%) while IOTA-LR2 exhibited the highest specificity (84.4%, 95% CI: 77.3−90%). Among the different serial test combinations, IOTA-LR1 with MIA2G and IOTA-LR2 with MIA2G showed the highest diagnostic accuracy (AUROC = 0.82). This study showed that all individual ultrasound-based models performed well in discerning malignant and benign ovarian lesions, with IOTA-LR1 exhibiting the highest accuracy.

Clinicopathologic Factors Associated with Mismatch Repair Status Among Filipino Patients with Young-Onset Colorectal Cancer.

INTRODUCTION: Young-onset colorectal cancer is recognized as a distinct disease that may be sporadic or hereditary in nature. Microsatellite instability testing is recommended as a routine procedure in evaluating colorectal cancer specimens, especially in young-onset disease, because of implications in management. Immunohistochemistry of mismatch repair proteins serves as an inexpensive alternative to microsatellite instability testing with the added advantage of monitoring protein expression levels that may suggest underlying genetic or epigenetic alterations. This descriptive study aimed to determine the frequencies of proficient and deficient mismatch repair status among Filipino young-onset colorectal cancer patients, and to investigate their clinicopathologic profile. METHODS: Tumor tissues were prospectively collected from patients from two tertiary hospitals in the Philippines. Patients of age ≤45 years with resected adenocarcinoma of the colon or rectum were recruited. RESULTS: Seventy-seven out of 124 patients had tumor samples sent for immunohistochemistry. Of these, 61 samples (79%) were found to have proficient status while 16 samples (21%) had deficient status. Mismatch repair protein deficiencies, when present, more commonly involved MSH2 and MSH6 (9%) rather than MLH1 and PMS2 (5%). The deficient group had a mean age of 37.1 years and a female preponderance (56.25%), presenting as locally advanced ascending or descending colon tumors with mucinous histology in half of the population. The mismatch repair proficient group presented as locally advanced rectal and sigmoid tumors but with fewer mucinous adenocarcinomas (26.2%) compared to the deficient group. In both the mismatch repair proficient and deficient patients with family history reports, most did not have any known relative with cancer (75.4% and 68.75%, respectively). CONCLUSION: This is the first attempt to perform mismatch repair testing among young-onset colorectal cancer patients in the Philippines and to gather data on their clinicopathologic characteristics. However, the limited sample size precludes conclusive results for the associations of mismatch repair with clinicopathologic features.

Utility of p57KIP2 and Her-2 fluorescence in situ hybridization in differentiating partial from complete hydatidiform mole

INTRODUCTION: Hydatidiform mole (HM) is an abnormal gestation characterized by significant hydropic enlargement, trophoblastic proliferation and atypia involving part or all of the chorionic villi. The diagnosis and classification of hydatidiform moles is subject to great inter-observer variability due to significant morphologic overlaps. This study aims to evaluate the utility of p57KIP2 immunohistochemistry and ploidy by Her-2 FISH in refining the diagnosis of molar tissues. METHOD: 113 and 78 molar cases were retrieved from the archives of the Histopathology Section of the Philippine General Hospital and Pathology Department of Seoul National University Hospital, respectively. TMA sections were submitted for immunohistochemical analysis for p57KIP2. Ploidy was determined by fluorescence in situ hybridization using Her-2 probe. An interrater reliability analysis was done using the Kappa statistics with 95% confidence interval. RESULTS: All 68 (100%) cases diagnosed as CH were negative for p57KIP2 staining and are diploid. Among the 54 cases of PH, only 1 (2%) is positive for p57KIP2 and is diploid. The interrater reliability between p57KIP2 and Her-2 FISH ploidy results is 0.66 (p CONCLUSION: Morphologic assessment alone may not be sufficient in problematic cases. p57KIP2 in conjunction with by Her-2 FISH are good adjuncts in the diagnosis and classification of hydatidiform mole.

Increased association of the ERG oncoprotein expression in advanced stages of prostate cancer in Filipinos.

BACKGROUND: Filipinos with prostate cancer (CaP) are at increased risk of harboring advanced stages and lower survival rates compared to other Asians. This study aims to investigate prevalence of ETS-related gene (ERG) oncoprotein overexpression in Filipinos as surrogate of TMPRSS2-ERG gene fusions, using a highly specific monoclonal antibody (ERG-MAb), and conduct the first attempt to study the role of genetic alterations in the aggressive tumor biologic behaviour of CaP among Filipinos. METHODS: This case-matched, case-control retrospective study evaluated ERG expression in Filipino patients diagnosed with CaP and its effect on stage and Gleason grade of their disease. Men who underwent radical prostatectomy for organ-confined disease at the University of the Philippines-Philippine General Hospital (UP-PGH) comprised the organ-confined cohort. Age-matched adults who had trans-rectal ultrasound-guided prostate (TRUSP) biopsy or trans-urethral resection of the prostate (TURP) with bilateral orchiectomy for T4 or stage IV CaP composed the advanced disease cohort. RESULTS: Overall ERG expression frequency of 23.08% (N = 104) was demonstrated, with a higher rate observed in the advanced disease cohort (32.69%) compared to the organ-confined group (13.46%). Furthermore, ERG overexpression was only detected among intermediate and high-risk tumors. A high-specificity (98.08%) of the ERG-MAb for malignant prostatic cells was likewise demonstrated. CONCLUSIONS: In contrast to higher ERG frequency in Western countries, it is much lower in Filipino CaP, which is similar to lower rates noted from other Asian countries. The 98.08% specificity of ERG oncoprotein for prostate tumor cells combined with its increased association in advanced disease, suggests for prognostic potential of ERG that may aid clinicians in treatment decisions for Filipino CaP patients.