Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer.

BACKGROUND: Recently, consensus molecular subtypes (CMSs) have been proposed as a robust transcriptome-based classification system for colorectal cancer (CRC). Tetraspanins (TSPANs) are transmembrane proteins. They have been associated with the development of numerous malignancies, including CRC, through their role as "master organizers" for multi-molecular membrane complexes. No previous study has investigated the correlation between TSPANs and CMS classification. Herein, we investigated the expression of TSPANs in patient-derived primary CRC tissues and their CMS classifications. METHODS: RNA samples were derived from primary CRC tissues (n = 100 patients diagnosed with colorectal adenocarcinoma) and subjected to RNA sequencing for transcriptome-based CMS classification and TSPAN-relevant analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) stains were conducted to observe the protein expression level. To evaluate the relative biological pathways, gene-set enrichment analysis was performed. RESULTS: Of the highly expressed TSPAN genes in CRC tissues (TSPAN8, TSPAN29, and TSPAN30), TSPAN8 was notably overexpressed in CMS3-classified primary tissues. The overexpression of TSPAN8 protein in CMS3 CRC was also observed by IHC and IF staining. As a result of gene-set enrichment analysis, TSPAN8 may potentially play a role in organizing signaling complexes for kinase-based metabolic deregulation in CMS3 CRC. CONCLUSIONS: The present study reports the overexpression of TSPAN8 in CMS3 CRC. This study proposes TSPAN8 as a subtype-specific biomarker for CMS3 CRC. This finding provides a foundation for future CMS-based studies of CRC, a complex disease and the second leading cause of cancer mortality worldwide.

Correction: The diagnostic performance of combined conventional cytology with smears and cell block preparation obtained from endoscopic ultrasound-guided fine needle aspiration for intra-abdominal mass lesions.

[This corrects the article DOI: 10.1371/journal.pone.0263982.].

The diagnostic performance of combined conventional cytology with smears and cell block preparation obtained from endoscopic ultrasound-guided fine needle aspiration for intra-abdominal mass lesions.

BACKGROUND/AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the primary method for tissue acquisition of intra-abdominal masses. However, the main limitation of cytology alone is the lack of tissue architecture and inadequate samples. This study aimed to evaluate the diagnostic performance of combined conventional cytology and cell block preparation obtained from EUS-FNA of intra-abdominal masses without Rapid On-site Evaluation (ROSE). METHODS: Cytologic smears and cell block slides of 166 patients undergoing EUS-FNA during 2010-2015 were reviewed by an experienced cytopathologist blinded to clinical data. RESULTS: 125 patients had neoplastic lesions. Pancreatic adenocarcinoma was the most common etiology (35.5%), followed by lymph node metastasis (27.7%). The mean mass size was 2.5±1.3 cm. The mean number of passes was 1.9±1.28. Tissue adequacy for conventional cytology and cell block preparation was 78.9% and 78.1%, respectively. Factors associated with tissue adequacy were assessed. For cytology, lesions of > 2.1 cm, masses in the pancreatic body or tail, malignancy, and pancreatic cancer were positively associated with adequate cellularity. For cell block preparation, lesions of > 3 cm and malignancy were associated with increased tissue adequacy. The conventional cytology alone had a sensitivity of 68.5%, a specificity of 95.7%, and an area under the receiver operating characteristics (AUROC) of 0.821. The cell block preparation alone had a sensitivity of 65.4%, a specificity of 96%, and an AUROC of 0.807. The combined conventional cytology and cell block preparation performed significantly better than either method alone (p<0.05), as demonstrated by an increased AUROC of 0.853. Furthermore, cell block detected malignancy in 9.3% of cases where the cytologic smears failed to identify malignant cells. CONCLUSIONS: The combined conventional cytology and cell block preparation increased the diagnostic accuracy of EUS-FNA compared to either method alone. This approach should be implemented in routine practice, especially where ROSE is unavailable.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Using 22G Franseen Needles without Rapid On-Site Evaluation for Diagnosis of Intraabdominal Masses.

BACKGROUND: The impact of rapid on-site cytologic evaluation (ROSE) on endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is widely debated. This study aims to assess the diagnostic performance of EUS-FNB in the absence of ROSE in abdominal masses. METHODS: Patients with abdominal masses undergoing EUS-FNB using 22-gauge Franseen needles and the slow-pull technique were prospectively enrolled in this study. Macroscopic on-site evaluation (MOSE) was performed without ROSE. RESULTS: 100 patients were recruited between 2018 and 2020. Seventy-eight patients had neoplasms, and twenty-two patients had benign diseases. Common diagnoses included pancreatic cancer (n = 27), mesenchymal tumors (n = 17), and metastatic tumors (n = 14). The mean mass size was 3.9 ± 2.6 cm. The median pass number was three. Eighty-nine percent had adequate specimens for histologic evaluation. Malignancy increased the odds of obtaining adequate tissue (OR 5.53, 95% CI, 1.36-22.5). For pancreatic cancer, FNB had a sensitivity of 92.3%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 97%, and an AUROC of 0.96. The sensitivity, specificity, PPV, NPV, and AUROC for mesenchymal cell tumors were 100%, 95.9%, 84.2%, 100%, and 0.98, respectively. For metastatic tumors, FNB was 100% sensitive and specific, with an AUROC of 1.00. There were no procedure-related complications. CONCLUSIONS: 22-gauge Franseen needles with the slow-pull technique and MOSE without ROSE provide excellent diagnostic performances for malignant lesions. Thus, MOSE should be implemented in real-world practice, and ROSE can be obviated when EUS-FNB is employed.

Gastrointestinal mucormycosis due to Rhizopus microsporus following Streptococcus pyogenes toxic shock syndrome in an HIV patient: a case report.

BACKGROUND: Gastrointestinal (GI) mucormycosis is a rare and often deadly form of mucormycosis. Delayed diagnosis can lead to an increased risk of death. Here, we report a case of GI mucormycosis following streptococcal toxic shock syndrome in a virologically suppressed HIV-infected patient. CASE PRESENTATION: A 25-year-old Thai woman with a well-controlled HIV infection and Grave's disease was admitted to a private hospital with a high-grade fever, vomiting, abdominal pain, and multiple episodes of mucous diarrhea for 3 days. On day 3 of that admission, the patient developed multiorgan failure and multiple hemorrhagic blebs were observed on all extremities. A diagnosis of streptococcal toxic shock was made before referral to Siriraj Hospital - Thailand's largest national tertiary referral center. On day 10 of her admission at our center, she developed feeding intolerance and bloody diarrhea due to bowel ischemia and perforation. Bowel resection was performed, and histopathologic analysis of the resected bowel revealed acute suppurative transmural necrosis and vascular invasion with numerous broad irregular branching non-septate hyphae, both of which are consistent with GI mucormycosis. Peritoneal fluid fungal culture grew a grayish cottony colony of large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. A complete ITS1-5.8S-ITS2 region DNA sequence analysis revealed 100% homology with Rhizopus microsporus strains in GenBank (GenBank accession numbers KU729104 and AY803934). As a result, she was treated with liposomal amphotericin B. However and in spite of receiving appropriate treatment, our patient developed recurrent massive upper GI bleeding from Dieulafoy's lesion and succumbed to her disease on day 33 of her admission. CONCLUSION: Diagnosis of gastrointestinal mucormycosis can be delayed due to a lack of well-established predisposing factors and non-specific presenting symptoms. Further studies in risk factors for abdominal mucormycosis are needed.