Clinicopathologic profile of intra-abdominal follicular dendritic cell sarcoma: A study of three cases with a literature review.

Follicular dendritic cell sarcoma (FDCS) is a rare tumor, which mainly originates from follicular dendritic cells (FDCs) in the lymph nodes. Sometimes FDCS can arise from outside the lymph nodes. FDCS is an extremely rare malignant tumor in intraperitoneal or retroperitoneal tissue. We gathered the detailed clinical data of three patients diagnosed with FDCS in the abdomen. The clinical observations and histopathologic and immunohistochemical features of FDCS were analyzed. The patients included two men and one woman aged 55 ~ 61 years old. The mesentery of the small intestine and colon was involved in case 1, spleen in case 2, and retroperitoneal tissues in case 3. Two patients presented with abdominal masses, and one presented with no obvious symptoms. Histology showed ovoid to spindle neoplastic cells arranged in fascicles and storiforms with inflammatory infiltrate as well as whorled patterns in some areas. Immunohistochemical staining was positive for CD21, CD23, CD35, and SSTR2. FDCS exhibits no characteristic clinical manifestations. Morphologically, FDCS can have overlapping features with many other entities, leading to misdiagnosis. The use of histopathology supplemented with FDC markers, such as CD21, CD23, and CD35, is useful for diagnosis and differential diagnosis.

Predictive Value of Clinicopathological Factors to Guide Post-Operative Radiotherapy in Completely Resected pN2-Stage III Non-Small Cell Lung Cancer.

Introduction: With the evolution of radiotherapy techniques and a better understanding of clinicopathological factors, we aimed to evaluate the treatment effect of post-operative radiotherapy (PORT) and associated predictive factors in patients with completely resected pN2 stage III non-small cell lung cancer (R0 pN2-stage III NSCLC). Material and Method: The cancer registration database of a single medical center was searched for R0 pN2-stage III NSCLC. Clinicopathological factors and information about post-operative therapies, including PORT and adjuvant systemic treatment, were retrospectively collected and analyzed. The Kaplan-Meier method and a Cox regression model were applied for time-to-event analysis, with disease-free survival (DFS) being the primary outcome. Results: From 2010 to 2021, 82 R0 pN2-stage III NSCLC patients were evaluated, with 70.1% of tumors harboring epidermal growth factor receptor mutations (EGFR mut.). PORT was performed in 73.2% of cases, and the median dose was 54 Gy. After a median follow-up of 42 months, the 3-year DFS and overall survival (OS) rates were 40.6% and 77.3%, respectively. Distant metastasis (DM) was the main failure pattern. In the overall cohort, DFS was improved with PORT (3-year DFS: 44.9% vs. 29.8%; HR: 0.552, p = 0.045). Positive predictive factors for PORT benefit, including EGFR mut., negative extranodal extension, positive lymphovascular invasion, 1-3 positive lymph nodes, and a positive-to-dissected lymph node ratio ≤0.22, were recognized. OS improvement was also observed in subgroups with less lymph node burden. Conclusions: For R0 pN2-stage III NSCLC, PORT prolongs DFS and OS in selected patients. Further studies on predictive factors and the development of nomograms guiding the application of PORT are highly warranted, aiming to enhance the personalization of lung cancer treatment.

Improving the detection of Helicobacter pylori in biopsies of chronic gastritis: a comparative analysis of H&E, methylene blue, Warthin-Starry, immunohistochemistry, and quantum dots immunohistochemistry.

Objectives: The objective of the study was to compare the consistency of various staining methods, including H&E, Methylene Blue, Warthin-Starry (W-S), Immunohistochemistry (IHC) and Quantum dots immunohistochemistry (QDs-IHC), in detecting Helicobacter pylori (HP) in cases of mild, moderate and severe chronic gastritis. Methods: Biopsy samples were obtained from 225 patients with chronic gastritis at the Department of Pathology, Yichang Central People's Hospital between January 2019 and October 2019. The presence of HP was detected using H&E, Methylene Blue, W-S, IHC, and QDs-IHC. Results: The positive rates for HP detection using H&E, Methylene Blue, W-S, IHC, and QDs-IHC were 42.22%, 51.11%, 53.78%, 59.11%, and 58.67%, respectively. In cases of mild chronic gastritis, the consistency of test results between H&E, Methylene Blue, W-S, and QDs-IHC with IHC were Kappa=0.196, P=0.033, Kappa=0.706, P<0.001, Kappa=0.717, P<0.001, and Kappa=0.968, P<0.001, respectively. Similarly, in cases of moderate chronic gastritis, Kappa values between H&E, Methylene Blue, W-S, and QDs-IHC with IHC were 0.356, P<0.001, 0.655, P<0.001, 0.741, P<0.001, and 0.946, P<0.001, respectively. For cases of severe chronic gastritis, the Kappa values between the staining methods and IHC were 0.271, P=0.037, 0.421, P=0.002, 0.621, P<0.001, and 1, P< 0.001, respectively. Conclusion: The study showed that the positivity rate of IHC was significantly higher than that of H&E, Methylene Blue, and W-S in detecting HP infection in chronic gastritis cases. In terms of consistency with IHC, QDs-IHC was the most reliable staining method across all severity grades, while the agreement between H&E and IHC was poor, and that between Methylene Blue and W-S with IHC was average. Pathology departments may choose the most appropriate staining method based on their specific needs, considering the staining time, contrast, and cost of each method.

Primary ectopic meningioma in the thoracic cavity: A rare case report and review of the literature.

Background: Meningioma is a common type of intracranial tumor in adults. It rarely arises in the chest, with only a few case reports in the English literature. Here, we report the case of a patient with a primary ectopic meningioma (PEM) located in the thoracic cavity. Case presentation: A 55-year-old woman presented with exercise-induced asthma, chest tightness, intermittent dry cough and fatigue for several months. Computed tomography revealed the presence of a huge mass in the thoracic cavity, with no connection to the spinal canal. Lung cancer and mesothelioma were suspected, and surgery was performed. Grossly, the mass was a grayish-white solid 9.5 cm × 8.4 cm × 5.3 cm in size. The microscopic morphology of the lesion was consistent with that of typical central nervous system meningioma. The pathological subtype was transitional meningioma. The tumor cells were arranged in a fascicular, whorled, storiform and meningithelial pattern, with occasional intranuclear pseudo-inclusions and psammoma bodies. In focal areas tumor cells were considerably dense, and the cells were round or irregular in shape, with less cytoplasm, uniform nuclear chromatin, and visible nucleoli and mitoses (2/10 HPF). By immunohistochemistry, the neoplastic cells showed strong and diffuse staining with vimentin, epithelial membrane antigen and SSTR2 with variable expression of PR, ALK and S100 protein. However, the cells were negative for GFAP, SOX-10, inhibin, CD34, STAT6, smooth muscle actin, desmin, CKpan, D2-40, WT-1, CK5/6 and CD45. The highest proliferation index by Ki-67 was 15%. The abnormal expression of ALK led to the initial misdiagnosis of an inflammatory myofibroblastic tumor. After 12 months of follow-up, no disease progression was observed. Conclusion: The presence of primary ectopic meningiomas in the thoracic cavity is extremely rare, and this tumor is easily misdiagnosed clinically. Imaging is suggested to determine the location and possible differential diagnosis, while the final diagnosis should be via pathological examination. Immunohistochemistry is crucial for disease diagnosis. Owing to our limited knowledge of PEM, its pathogenesis and tissue of origin remain unclear. Clinicians should pay close attention to such potential patients. The present case report may provide insights into the diagnosis and therapy of patients with this tumor.

Myoepithelioma-like tumors of the vulvar region: A case report and review of the literature.

Myoepithelioma-like tumors of the vulvar region (MELTVR) is a kind of solid tumor newly recognized in recent years, which is characterized by mesenchymal tumors of adult female vulva. The histopathology is similar to myoepithelioma, but the immunohistochemical phenotype and genetic changes are different from myoepithelioma. It usually has clear boundary and partial capsule, mixed with two forms of cells (epithelioid and spindle), the cells are mild, the nucleoli are clear, mitoses are rare, some cases have myxoid differentiation. In this article, a case of MELTVR diagnosed in our hospital is discussed. The patient was a 43-year-old female who finds a neoplasm in the pubic tubercle 4 months ago. Local resection was performed. Pathological examination showed that the boundary of the tumor was clear with partial capsule. The cells were arranged in cords or nests, and partially infiltrated the surrounding adipocytes. The tumor cells had two morphologies, epithelioid or spindle shaped. The spindle type cells were dominant, with bright cytoplasm, obvious nucleoli, rare nuclear mitosis (about 1/10HPF), and no necrosis was observed. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, estrogen receptor, progestogen receptor, calponin and were partially positive for cathepsin k. INI1/SMARCB1 expression was deficient. There was no recurrence or metastasis during the 8-month-long follow-up. The unique feature of this case was that the site of the disease was not the vulva, but in front of the pubic tubercle, there was no large amount of mucus production, and the cytoplasm of most tumor cells was transparent. Due to our limited knowledge of MELTVR, its pathogenesis and tissue origin are not clear. Clinicians should be aware of such potential patients.

High Superior-Middle Pharyngeal Constrictor Muscle Mean Dose Correlates with Severe Late Lung Infection and Survival in Nasopharyngeal Cancer Patients.

Purpose: The study aimed to evaluate 1) the correlation of doses of swallowing-related organs at risk (OAR) with severe swallowing-related late adverse effects (AE) in nasopharyngeal carcinoma (NPC) patients and 2) the effect of high mean doses of OARs on overall survival (OS). Patients and Methods: This retrospective cohort study enrolled non-metastatic Stage I-IV NPC patients from January 2012 to June 2017. OAR mean doses and severe (≥G3) swallowing-related late AE (xerostomia, dysphagia, and lung infection) were evaluated by t-test and validated using receiver operating characteristic curves. The risk factors of OS were calculated by Cox regression methods. Results: This study enrolled 185 (43 female, 142 male) NPC patients, mean age 52.4 years, primarily with Stage III (93, 50.3%) or Stage IV (67, 36.2%) disease. The mean doses of pharyngeal constrictor muscle (PCM), superior-middle PCM (SMPCM), and superior PCM (SPCM) were significantly higher in those with severe (≥G3) lung infection than in those without (65.7 vs 62.2 Gy, p = 0.036; 68.1 vs 64.2 Gy, p = 0.015; and 70.0 vs 65.9 Gy, p = 0.012, respectively). Patients with severe (≥G3) dysphagia had significant higher mean doses of base of tongue (56.2 vs 50.2 Gy, p = 0.008), laryngeal box (50.6 vs 46.4 Gy, p = 0.036), PCM (65.4 vs 62.1 Gy, p = 0.008), SMPCM (67.1 vs 64.2 Gy, p = 0.014), and SPCM (69.3 vs 65.8 Gy, p = 0.004). Mean SMPCM dose >64.9 Gy (adjusted hazard ratio [aHR] = 3.2, 95% confidence interval [CI] 1.2-8.8, p = 0.021), age >62 years (aHR = 2.7, 95% CI 1.1-6.9, p = 0.032), N3 status (aHR = 4.0, 95% CI 1.8-9.0, p = 001), and severe late AE of lung infection (aHR = 4.6, 95% CI 1.5-14.0, p = 0.007) significantly affected OS. Conclusion: Severe lung infection and dysphagia were associated with significantly higher mean doses of PCM, SMPCM, and SPCM. Among these OARs, only a high SMPCM mean dose was a risk factor for OS in NPC patients.

Pediatric Extraspinal Subcutaneous Sacrococcygeal Myxopapillary Ependymoma: Case Report and Minireview.

ABSTRACT: A 9-year-old girl presented with a slow-growing and painless mass for 7 months in the soft tissue of the sacrococcygeal region. Magnetic resonance imaging revealed a well-circumscribed solid mass located in the subcutaneous soft tissue of the sacrococcygeal area, but not affecting bone structures. The mass was completely removed, and the disorder was diagnosed as myxopapillary ependymoma. In addition, the MYCN gene amplification status of the tumor was evaluated. Extra-axial ependymomas are very rare tumors with a tendency to metastasis, but they are usually regarded as low-grade ependymomas. Long-time surveillance and follow-up are necessary even after complete excision. Besides, we also discuss the diagnosis of primary soft tissue myxopapillary ependymoma.

Disseminated peritoneal leiomyomatosis: a case report and review of the literature.

Disseminated peritoneal leiomyomatosis (DPL), also known as leiomyomatosis peritonealis disseminata, is a rare disease characterized by multiple benign smooth muscle tumors proliferating along the peritoneal surfaces. The cause of the disease is unclear, and possible factors include iatrogenic and hormonal stimulation. The patient was a 41-year-old Chinese woman with a history of laparoscopic myomectomy and subsequent pregnancy. Multiple abdominal masses were identified and required surgical intervention. The patient had no tenderness or other discomfort. The clinical and imaging diagnosis was gastrointestinal stromal tumor, but DPL was confirmed by postoperative pathological examination. The patient had a good prognosis, and no recurrence was observed during follow-up. Iatrogenic and hormonal stimulation leading to DPL is very rare, and we believe that multiple factors led to DPL in this case. Clinicians should be aware of such potential patients.

Contralateral lymph node recurrence rate and its prognostic factors in stage IVA-B well-lateralized oral cavity cancer.

PURPOSE: To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. MATERIALS AND METHODS: Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. RESULTS: From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. CONCLUSIONS: Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

Comparison of quantum dot immunofluorescence histochemistry with conventional immunohistochemistry in detecting Helicobacter pylori infection in paraffin-embedded tissues of gastric biopsy.

Quantum dots (QDs) are a new type of fluorescent label, which has been widely used in many biological and biomedical imaging applications. In this study, we used QDs-based immunofluorescence histochemistry (QDs-IHC) and conventional immunohistochemistry (IHC) techniques to perform a retrospective analysis on paraffin-embedded tissues of gastric biopsies in 203 patients (112 of which were HP positive and 91 were negative). The ability of QDs-IHC to detect Helicobacter pylori (HP) in gastric biopsies compared to IHC technology was evaluated. In our study, both methods showed consistent HP morphology and localization. The positive detection rate of HP for QDs-IHC in formalin-fixed and paraffin-embedded (FFPE) tissue was 54.7% (111/203), and the sensitivity and specificity reached 99.11% and 100%, respectively. However the positive detection rate of HP for IHC was 53.7% (109/203), with a sensitivity and specificity of 97.32% and 100%, respectively. Weak positives (1+) were detected in 2 case of QDs-IHC with negative in IHC, and moderate positives (2+) were detected in 3 case of QDs-IHC with weak positives (1+) in IHC. The consistency test showed that the two methods showed good agreement (κ = 0.980, P = 0.014), but the sensitivity of QDs-IHC was slightly higher than that of conventional IHC. Our results show that QDs-IHC has strong sensitivity and high specificity. It is superior to conventional IHC in detecting HP infection in FFPE tissues of gastric biopsy, especially in tissues with low HP content.

Simultaneous Reduction of Volume and Dose in Clinical Target Volume for Nasopharyngeal Cancer Patients.

PURPOSE: To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods. RESULTS: From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P < .001) and salvage survival (79.3% vs 20.7%; P < .01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007). CONCLUSIONS: Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits.

Ductal Carcinoma In Situ of the Breast: Perspectives on Tumor Subtype and Treatment.

OBJECTIVE: To evaluate ductal carcinoma in situ (DCIS) characteristics and the effect of different treatment strategies. Patients and Methods. Using data with known hormone receptor (HoR) and human epidermal growth factor receptor 2 (HER2) status obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2014, the study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM). RESULTS: A total of 3415 patients with DCIS were eligible. Compared with HoR+/HER- subgroup, patients with triple-negative (TN) and HoR-/HER+ were commonly higher in grade, larger in size, and tended to receive mastectomy (P < 0.05). The multivariate analysis revealed that patients with TN were more likely to have a poorer OS and show a higher breast cancer-specific mortality compared with the HoR+/HER- subgroup (P < 0.05). Multivariate analysis on the history of local treatment and surgery showed patients receiving breast-conserving surgery (BCS) plus radiotherapy (R) and BCS plus axillary lymph node dissection was likely to improve OS without affecting breast cancer-specific mortality (P < 0.05). CONCLUSION: The results demonstrate that DCIS associated with TN subtype portends poor prognosis. Meanwhile, BCS plus R was a preferable option and resulted in survival rates better than those achieved with mastectomy, and SLNB should be considered as an appropriate assessment of axillary staging in patients with DCIS.

Xanthium strumarium Fruit Extract Inhibits ATG4B and Diminishes the Proliferation and Metastatic Characteristics of Colorectal Cancer Cells.

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA2. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells.

Which nasopharyngeal cancer patients need adaptive radiotherapy?

BACKGROUND: Adaptive radiotherapy (ART) has potential benefits in patients with nasopharyngeal cancer (NPC). This retrospective study aimed to identify the factors favoring ART. MATERIALS AND METHODS: Forty NPC patients were retrospectively included in this study. All patients received two-phase, volumetric modulated arc radiotherapy (VMAT) and underwent a second computed tomography (CT) for the phase II ART. We generated phantom, non-ART plans by a hybrid method for comparison with ART plans. A paired t-test was used to evaluate the dose differences between these two plans. A subgroup analysis through a paired t-test was used to evaluate the factors favoring ART. RESULTS: The second CT images were captured at the median 22 fractions. The median total dose of the planning target volume-one (PTV-1) was 72 Gy, and the phase II dose was 16 Gy. The volumes of the ipsilateral parotid gland (23.2 vs. 19.2 ml, p <  0.000), contralateral parotid gland (23.0 vs. 18.4 ml, p <  0.000), clinical target volume-1 (CTV-1, 32.2 vs. 20.9 ml, p <  0.000), and PTV-1 (125.8 vs. 107.3 ml, p <  0.000) all shrunk significantly between these two CT simulation procedures. Among the nearby critical organs, only the ipsilateral parotid gland displayed significant dose reduction by the ART plan (5.3 vs. 6.0 Gy, p = 0.004). Compared to the phantom plan, the ART could significantly improve the PTV-1 target volume coverage of D98 (15.4 vs. 12.3 Gy, p < 0.000). Based on the D98 of PTV-1, the factors of a large initial weight (> 60 kg, p < 0.000), large body mass index (BMI) (> 21.5, p < 0.000), obvious weight loss (> 2.8 kg, p < 0.000), concurrent chemoradiotherapy (p < 0.000), and stages III-IV (p < 0.000) favored the use of ART. CONCLUSIONS: ART could significantly reduce the mean dose to the ipsilateral parotid gland. ART has dosimetrical benefit for patients with a heavy initial weight, large BMI, obvious weight loss, concurrent chemoradiotherapy, and cancer in stages III-IV.

Comparative testing of HPV L1 protein monoclonal antibody panel for the detection of HPV in cervical exfoliated cells.

AIMS: To determine the value of a monoclonal antibody panel against a C-terminal conserved sequence polypeptide of human papillomavirus (HPV) L1 (a major capsid protein) for the detection of HPV in cervical exfoliated cells, as well as the potential of this antibody panel to be developed into an assay kit for the clinical screening of cervical cancer. METHODS: Cervical exfoliated cells were collected at a gynecology clinic. One part of each sample was sent to the Department of Pathology for HPV genotyping, and the other part was sent to the Department of Pathology for cytologic testing and then to the laboratory for immunological histological chemistry (IHC) assay in which an HPV L1 C-terminal conserved sequence polypeptide-induced mouse monoclonal antibody panel was used to detect HPV L1. RESULTS: Cervical cell samples were collected from 514 patients at the gynecology clinic; of these, 339 samples were sent for HPV genotyping, and 220 were HPV positive (64.90%, 220/339). Moreover, the duplicate samples from these 339 patients were sent for IHC assay, and 229 samples were positive (67.55%, 229/339). The IHC result was concordant with that obtained by HPV genotyping (Kappa = 0.743, p < 0.001). CONCLUSION: This study showed that use of the HPV L1 C-terminal conserved sequence polypeptide-induced mouse monoclonal antibody panel was of great value for the detection of HPV in cervical cells; the resulting detection rate was comparable to that obtained using the commercial HPV genotyping kit that is currently in use in clinical practice.

Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma.

Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p<0.001). The expression level of caspase-8 in tumors was elevated in patients with lymph node invasion. Moreover, positive expression of cleaved caspase-3 was associated with shorter disease-free survival (DFS) in OTSCC patients with moderate differentiation and lymph node invasion. Combination of either positive cleaved caspase-3 or higher caspase-3 expression or both was associated with poor DFS. Interestingly, stratification analysis showed that co-expression levels of positive cleaved caspase-3 or/and higher caspase-3 were associated with better disease-specific survival in patients with advanced stages of the disease, such as large tumor size and lymph node invasion, whereas it was associated with poor DFS in OTSCC patients with moderate cell differentiation and small tumor size. Taken together, cleaved caspase-3 and caspase-3/8/9 could be biomarkers for tumorigenesis in OTSCC patients. The co-expression level of cleaved caspase-3 and caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those patients with certain tumor stages and cell differentiation status.

Hyalinizing trabecular tumor of the thyroid: a clinicopathological analysis of four cases and review of the literature.

OBJECTIVE: To explore the clinicopathological features, diagnosis and differential diagnosis of hyalinizing trabecular tumor (HTT) of the thyroid. METHODS: The four HTT specimens were collected including demographics, clinical information, relevant images, the extent of thyroidectomy, the follow-up and representative pathological data of tumors were available for analysis. In addition, the immumohistochemical staining related to the tumor as well as the BRAF and N-ras mutation analysis were analysed. RESULTS: The mean age of four patients was 47 years old and the mean size of the tumor was 2.8 cm. Most of the patients were asymptomatic, while detecting incidentally by using neck ultrasound test. Ultrasound imaging of all cases showed demarcated substantial hypoechoic nodules in ipsilateral thyroid lobe. Computed Tomography (CT) showed a clear low density shadow in the affected thyroid lobe. Tumors of three cases were located at the left, but the other one was located at the right thyroid gland with a complete fibrous capsule. The cytological features resembled papillary thyroid carcinoma (PTC). The histological test indicated that the tumors had characteristic of trabecular growth pattern with hyalinizing material. The tumor cells were in shape of polygonal, oval or high columnar with an acidophilic or clear cytoplasm. The nuclei were oval with inconspicuous small nucleoli, prominent grooves and pseudoinclusion body in cell nucleus. Mitosis and psammoma bodies were rare to be observed. Cytoplasmic "yellow bodies" were frequently observed. The hyaline material was prominent, with positive periodic acid-Schiff (PAS) and negative Congo red staining. Immunohistochemically, tumor cells were positive for thyroglobulin (Tg), thyroid transcription factor-1 (TTF-1), CD56 and negative for calcitonin, cytokeratin 19 (CK19), HBME-1, S-100 and synaptophysin (SyN). Chromogranin A (CgA) and galectin-3 were expressed weakly in some cases. Staining with the MIB-1 antibody showed membranous/cytoplasmic immunoreactivity. Whereas, another clone of Ki-67 (SP6) showed a common nuclear pattern with an index of <1%. None of the four cases exhibited the BRAF V600E protein reactivity. Gene mutation analysis demonstrated no BRAF and N-ras mutation. There was no evidence of local recurrence or metastasis after 6 to 36 months of follow-up. CONCLUSIONS: HTT is an uncommon thyroid tumor with very low malignant potential. It has no particular clinical features, so it's often misdiagnosed in fine needle aspiration cytology (FNAC)/Ultrasonography-guided fine needle aspiration cytology (US-FNAC) and frozen section (FS). Its final diagnosis mainly relies on typical histopathological features and characteristic expression pattern of MIB-1 immunohistochemical staining.

Curcumin inhibits growth of human breast cancer cells through demethylation of DLC1 promoter.

The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. A tumor suppressor Deleted in Liver Cancer 1 (DLC1) has been reported to be down-regulated or even silenced in several kinds of cancer including breast cancer. Curcumin has been reported to modulate the growth of tumor cells through regulation of multiple cell signaling pathways and modulate epigenetic changes by CpG demethylation of many tumor suppressor genes. This study was designed to investigate the effect of curcumin on the expression of Deleted in Liver Cancer 1 (DLC1) in human breast cancer cell line MDA-MB-361 and the underlying mechanism in vitro and in vivo. Curcumin induced DLC1 expression in a dose-dependent manner. In curcumin-treated cells, methylation of DLC1 promoter was reduced and active forms of RhoA and Cdc42 were also decreased. DLC1 expression was closely related to tumor cell growth, demonstrated by Ki67 staining. Curcumin inhibited DNA methyltransferase 1 expression through down-regulation of transcription factor Sp1. Consistent with the in vitro data, in vivo administration of curcumin inhibited the growth of implanted MDA-MB-361 cells and induced DLC1 expression in tumor tissue. In MDA-MB-361 cells, curcumin down-regulates the expression of Sp1 to inhibit the expression of DNA methyltransferase 1, thus subsequently reducing hypermethylation of DLC1 promoter to induce DLC1 expression.

CARP is a potential tumor suppressor in gastric carcinoma and a single-nucleotide polymorphism in CARP gene might increase the risk of gastric carcinoma.

BACKGROUND: The caspase-associated recruitment domain-containing protein (CARP) is expressed in almost all tissues. Recently, the tumor-suppressive function of CARP was discovered and attracted increasing attention. This study aimed to investigate the role of CARP in the carcinogenesis of human gastric carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Compared with normal gastric tissue, the downregulation of CARP expression was observed in gastric carcinoma tissue by cDNA array and tissue microarray assay. In vitro, the gastric carcinoma cell line (BGC-823) was stably transfected with pcDNA3.1B-CARP or plus CARP siRNA, and we used MTT, flow cytometry, cell migration on type I collagen, cell-matrix adhesion assay and western blot analysis to investigate the potential anti-tumor effects of CARP. The data showed that overexpressing CARP suppressed the malignancy of gastric carcinoma BGC-823 cell line, including significant increases in apoptosis, as well as obvious decreases in cell proliferation, migration, adhesion ability, and tumor growth. The tumor-suppressive effects of CARP were almost restored by siRNA-directed CARP silence. In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21. In vivo, the tumor-suppressive effect of CARP was also verified. A single-nucleotide polymorphism (SNP) genotype of CARP (rs2297882) was located in the Kozak sequence of the CARP gene. The reporter gene assay showed that rs2297882 TT caused an obvious downregulation of activity of CARP gene promoter in BGC-823 cells. Furthermore, the association between rs2297882 and human gastric carcinoma susceptibility was analyzed in 352 cases and 889 controls. It displayed that the TT genotype of rs2297882 in the CARP gene was associated with an increased risk of gastric carcinoma. CONCLUSIONS/SIGNIFICANCE: CARP is a potential tumor suppressor of gastric carcinoma and the rs2297882 C>T phenotype of CARP may serve as a predictor of gastric carcinoma.