Identification of SERPINA1 promoting better prognosis in papillary thyroid carcinoma along with Hashimoto's thyroiditis through WGCNA analysis.

Background: Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease. Papillary thyroid carcinoma (PTC) is the most common endocrine cancer. In recent years the rate of coexistence between PTC and HT has increased but the relationship between them remains unclear, meaning it is necessary to find potential biomarkers for PTC coexistence with HT to predict its potential pathways. Method: A co-expression network was constructed using the weighted gene co-expression network analysis (WGCNA) in the R package. The modules of PTC associated with HT (PTC-W) were identified from the GSE138198 dataset. Protein-protein interaction network (PPI) was used to screen the hub genes. Immunohistochemical (IHC) analysis was performed to validate the expression of the hub genes in tissues. Clinical data from The Cancer Genome Atlas (TCGA) datasets were used to analyse the prognosis of the hub genes. Gene set enrichment analysis (GSEA) was used to screen potential pathways of PTC-W. Result: The MEbrown module representing the most significant module, with 958 differentially expressed genes (DEGs), was screened in PTC-W, based on WGCNA analysis. Through PPI, SERPINA1 was identified as a hub gene. Immunostaining validated that SERPINA1 was highly expressed in PTC-W. Moreover, PTC-W expressing SERPINA1 exhibits a better prognosis than PTC without HT (PTC-WO). Conclusion: Our study demonstrates that SERPINA1 promotes the occurrence of PTC-W, and its prognosis is better than PTC-WO. SERPINA1 promotes a better prognosis for PTC-W, possibly through a tumour inhibition signalling pathway.

Comparative analysis of clinicopathological characteristics of central necrotizing breast cancer and basal cell-like breast cancer.

Purpose: This study aims to compare the clinicopathological and immunohistochemical characteristics of centrally necrotizing carcinoma of the breast (CNC) and basal-like breast cancer (BLBC), as well as to analyze the characteristics of the molecular typing of the CNC. Methods: The clinicopathological features of 69 cases of CNC and 48 cases of BLBC were observed and compared. EnVision immunohistochemical staining was performed to detect the expressions of hypoxia-inducible factor 1α (HIF-1α), breast cancer susceptibility gene 1 (BRCA1), and vascular endothelial growth factor (VEGF) in CNC and BLBC. Results: The age of the 69 patients ranged from 32 to 80 years, with an average of 54.55 years. Gross examination showed that most tumors were well-defined single central nodules with a diameter of 1.2~5.0 cm. Microscopically, there is a large necrotic or acellular area in the center of the tumor, mainly composed of tumor coagulative necrosis with varying degrees of fibrosis or hyaline degeneration. A small amount of cancer tissue remained in the form of a ribbon or small nest around the necrotic focus. Among 69 cases of CNC, the proportion of basal cell type (56.5%) was significantly higher than that of lumen type A (18.84%), lumen type B (13.04%), HER2 overexpression (5.8%), and nonexpression (5.8%). A total of 31 cases were followed up for 8~50 months, with an average of 33.94 months. There have been nine cases of disease progression. When compared to BLBC, there were no significant differences in BRCA1 and VEGF protein expression in response to CNC (p > 0.05), but there were significant differences in protein expression in HIF-1α (p < 0.05). Conclusion: The molecular typing of CNC showed that over half of those were BLBC. No statistically significant difference in the expression of BRCA1 was observed between CNC and BLBC; thus, we predict that targeted therapy for BRCA1 in BLBC may also have considerable effects in CNC patients. The expression of HIF-1α is significantly different in CNC and BLBC, and perhaps HIF-1α can be used as a new entry point to distinguish between the two. There is a significant correlation between the expression of VEGF and HIF-1α in BLBC, and there was no significant correlation between the expression levels of the two proteins in CNC.

Glucoside xylosyltransferase 2 as a diagnostic and prognostic marker in gastric cancer via comprehensive analysis.

To investigate the potential role of GXYLT2 (glucoside xylosyltransferase 2) in gastric cancer (GC), the TCGA (The Cancer Genome Atlas) database and Gene Expression Omnibus (GEO) dataset were used to evaluate GXYLT2 mRNA expression, and the standardized mean difference and diagnostic value were comprehensively assessed. Survival analysis and univariate/multivariate cox regression analysis were performed to evaluate the prognostic value of GXYLT2 in GC patients. The correlation between GXYLT2 and tumor immune cells was identified by using the CIBERSORT algorithm. The results showed that GXYLT2 expression level was significantly increased in GC tissues. GXYLT2 expression was significantly correlated with the grade, stage, and invasion depth of gastric cancer. Overall survival was reduced in the high GXYLT2 expression group. Univariate and multivariate Cox regression analyses showed that GXYLT2 was a reliable prognostic factor. GSEA showed that GXYLT2 might participate in the development of GC through tumor-related pathways. The expression of GXYLT2 was positively correlated with 5 tumor-infiltrating immune cells (resting dendritic cells, m2 macrophages, monocytes, active NK cells and resting mast cells), and was negatively correlated with 6 tumor-infiltrating immune cells (plasma cells, activated memory CD4 T cells, resting NK cells, activated dendritic cells, and activated neutrophils and mast cells). Through cell experiment verification, GXYLT2 expression level in gastric cancer cells was found to be high, which verified the results from the bioinformatics analysis. Furthermore, immunohistochemical staining results also showed that GC tissues had positive GXYLT2 expression. In summary, GXYLT2 might be a potential diagnostic and prognostic biomarker for gastric cancer.

Clinicopathological features of superficial CD34-positive fibroblastic tumor.

BACKGROUND: Superficial CD34-positive fibroblastoma (SCPFT) is a newly discovered mesenchymal tumor characterized by high polymorphism, low mitotic rate, and diffuse CD34-positive reactions. AIM: To further determine the clinicopathological features of SCPFT. METHODS: We retrospectively analyzed the clinicopathological data, immunohistochemistry results, and differential diagnoses of four patients with SCPFT and performed a literature review. Relevant fusion genes were also detected. RESULTS: The tumors were all located in the lower extremities and presented as slow-growing painless masses located in the dermis and subcutaneous tissue. Microscopically, the tumors were composed of spindle-shaped to epithelioid cells with scattered abnormal and pleomorphic nuclei on a fibrous or fibromyxoid background. Necrosis was not found in the tumor tissues, and mitotic figures were rare. Immunohistochemically, the tumor cells were strongly positive for vimentin and CD34, and CKpan showed focal positivity in two tumors. All four patients were followed (13-57 mo, mean 35 mo), and one patient experienced local recurrence. CONCLUSION: SCPFT is a newly discovered borderline mesenchymal tumor that can locally recur or even metastasize. Familiarity with its clinicopathological features will help avoid confusion with skin mesenchymal tumors with similar features.

Fluorescence in situ hybridization for WWTR1-CAMTA1 has higher sensitivity and specificity for epithelioid hemangioendothelioma diagnosis.

Epithelioid hemangioendothelioma (EHE) is a rare medium-to-low-grade malignant vascular tumor characterized by vascular differentiation along with specific morphological and genetic alterations. Approximately 90% and 5% of EHE cases are associated with the WWTR1-CAMTA1 and YAP1/TFE3 fusion gene, respectively. Therefore, nuclear CAMTA1 protein expression is considered to be an effective marker for EHE diagnosis. However, the specificity and reliability of this approach have recently been put into question. The purpose of this study was to compare the detection of CAMTA1 expression in cases of EHE and histologic mimics using fluorescence in situ hybridization (FISH) and conventional protein immunohistochemistry via hematoxylin and eosin staining. Fifteen EHE and 37 histologic mimic samples were immunohistochemically stained with polyclonal anti-CAMTA1 antibody to evaluate the nuclear protein expression level of CAMTA1. In addition, 15 EHE samples and 10 vascular tumor samples were subjected to FISH to detect the WWTR1-CAMTA1 fusion gene. Histologically, EHE typically showed a mucous hyaline or cartilaginous stroma, often forming a primitive vascular lumen, and expressed vascular endothelial markers. Twelve of the 15 EHE samples showed positive nuclear CAMTA1 expression with immunohistochemistry, whereas six of the 37 histologic mimics showed positive nuclear expression. FISH detected a red-green signal fusion in 14 of the 15 cases of EHE, but in none of the 10 vascular tumors. These results indicate that CAMTA1 is an effective and useful EHE marker, but that FISH fusion gene detection has better diagnostic value and clinical significance.

Chaperone-mediated Autophagy Governs Progression of Papillary Thyroid Carcinoma via PPARγ-SDF1/CXCR4 Signaling.

CONTEXT: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Chaperone-mediated autophagy (CMA), 1 type of autophagy, is thought to promote or suppress cancer development in different cancer types. However, the effect of CMA on PTC development and the underlying mechanisms remain unknown. OBJECTIVE: To determine whether CMA plays implied critical roles in the development of PTC. DESIGN: We investigated the association between CMA and PTC development in PTC tissues and normal thyroid tissues by detecting the key protein of CMA, lysosome-associated membrane protein type 2A (LAMP2A), using quantitative polymerase chain reaction (PCR) and immunohistochemistry, which were further validated in the TGCA dataset. The effect of CMA on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanisms of peroxisome proliferator-activated receptor γ (PPARγ)-stromal cell-derived factor 1 (SDF1)/ C-X-C motif chemokine receptor 4 (CXCR4) signaling were clarified by western blotting, quantitative PCR, and rescue experiments. Knockdown and tamoxifen were used to analyze the effect of estrogen receptor (ER) α on CMA. RESULTS: Our study confirmed that CMA, indicated by LAMP2A expression, was significantly increased in PTC tumor tissues and cell lines, and was associated with tumor size and lymph node metastasis of patients. Higher CMA in PTC promoted tumor cell proliferation and migration, thereby promoting tumor growth and metastasis. These effects of CMA on PTC were exerted by decreasing PPARγ protein expression to enhance SDF1 and CXCR4 expression. Furthermore, CMA was found positively regulated by ERα signaling in PTC. CONCLUSION: Our investigation identified CMA regulated by ERα promoting PTC tumor progression that enhanced tumor cell proliferation and migration by targeting PPARγ-SDF1/CXCR4 signaling, representing a potential target for treatment of PTC.

Clear cell sarcoma of the kidney in children: a clinopathologic analysis of three cases.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare malignant tumor in children with uncertain histologic and immunohistologic traits. It mostly reveals atypical clinical symptoms similar to other familiar pediatric renal neoplasms, including abdominal mass, abdominal pain, hematuria, etc. Therefore, the lack of specificity in clinical symptoms may induce some challenging and controversial diagnoses. METHODS: Three cases of CCSK were acquired data from the First Affiliated Hospital of Bengbu Medical College (China) in recent years, accompanied by clinical symptoms and imaging manifestations without obvious specificity, while abdominal mass and abdominal pain were described as the main manifestations; even the initial clinical diagnosis of one case was Wilms Tumor (WT). Two of them underwent a radical nephrectomy. All 3 cases were detected by hematoxylin-eosin (H&E) staining and immunohistochemistry. RESULTS: Microscopic examination demonstrated the tumor component consisted of loose, locally dense tumor stroma and parenchyma composed of round or oval cells, which were separated by dendritic fibrosis. Afterwards, the unified immunophenotype were positive for Cyclin D1, Bcl-2, Vimentin, SATB-2, α-AACT, and Ki-67 (+, 30%, 40% and 80%, respectively). CONCLUSION: Pathologic diagnosis of the disease should be comprehensively analyzed by multiple methods. More abundant morphologic, immunohistological, clinical and radiologic data can contribute to rigorous diagnosis and more accurate clinical treatment.

LPS-induced CXCR7 expression promotes gastric Cancer proliferation and migration via the TLR4/MD-2 pathway.

BACKGROUND: Lipopolysaccharide (LPS) from Helicobacter pylori (HP) plays an important role in gastric cancer occurrence and development. Toll-like receptor 4 (TLR4) and myeloid differential protein-2 (MD-2) are also reported to be involved in gastric cancer cell proliferation and invasion. CXC chemokine receptor 7 (CXCR7), a second receptor for CXCL12, has been detected in multiple types of tumor tissues. Nevertheless, the biological function and regulation of CXCR7 and its relationship with TLR4 and MD-2 in gastric cancer are not completely understood and therefore warrant further study. METHODS: CXCR7 expression was examined in 150 gastric cancer tissues using immunohistochemistry (IHC). RT-PCR and western blotting were used to detect CXCR7 expression in several gastric cancer cell lines (SGC7901, AGS, MGC-803, MKN-45 and BGC823). shRNAs were designed using a pGPU6/GFP/Neo vector. A CCK-8 assay was used to assess cell proliferation, and transwell assays were performed to assess cell migration. In addition, a gastric cancer xenograft model was generated. RESULTS: The LPS-TLR4-MD-2 pathway elevates CXCR7 expression in SGC7901 cells, and TLR4/MD-2-mediated increases in CXCR7 levels modulate the proliferation and migration of tumor cells. Knockdown of TLR4 and MD-2 demonstrated that both are essential for LPS-induced CXCR7 expression, which in turn is responsible for LPS-induced SGC7901 cell proliferation and migration. Moreover, higher TLR4, MD-2 and CXCR7 expression was detected in gastric cancer tissues than in paracancerous normal control tissues. The expression levels of TLR4, MD-2 and CXCR7 were closely related to gastric cancer TNM stage and lymph node metastasis. In an animal model, significant differences in CXCR7 expression in tumor masses were observed between the control group and experimental group. CONCLUSIONS: The results of this study indicate that CXCR7 plays an important role in gastric cancer progression via inflammatory mechanisms, suggesting that CXCR7 could provide a basis for the development and clinical application of a targeted drug for gastric cancer.

Mammary analogue secretory carcinoma of the minor salivary gland: report of two cases.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour notable for a balanced chromosomal translocation t(12;15)(p13;q25) that contributes to ETV6 gene rearrangements. It was first reported in 2010 by Skalova et al. with histological features resembling secretory carcinoma of the breast and was acknowledged and referred to as "secretory carcinoma" in the updated 2017 WHO classification. It is reported that MASC accounts for <0.3% of all salivary gland tumours, with a finite number of published reports on it. MASC has a range of histological features and clinical behaviours. The histopathological diagnosis of MASC can be difficult with current immunohistochemical methods. One case was located in the left palate, and 1 case was located in the soft palate. The maximum diameter of the tumour was 1.4~3.7 cm. CT demonstrated a mass that had not invaded into the palate bone, and the patients underwent palate neoplasm expanded ectomy without neck dissection or postoperative radiation therapy. Histopathological examination revealed that the tumour cells consisted of a mixed arrangement of microcystic, papillary-cystic, follicular, and solid lobular growth patterns. Eosinophilic cytoplasm and intraluminal or intracytoplasmic colloid-like secretions were observed. The final pathology confirmed the diagnosis of MASC with immunohistochemically neoplastic cells staining positive for S-100 and mammaglobin. The patients were asymptomatic at their 12-month follow up. More studies are needed to identify the typical behaviour of this tumour and establish the standard treatment regimen. This study aims to reinforce the awareness of this tumour by analysing its clinicopathologic features, immunophenotype, and diagnosis.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT): a challenge for clinicopathological diagnosis.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an extremely aggressive ovarian tumor, with a poor prognosis and high mortality for young women. This paper aims to inform clinical physicians of new clinical improvements and further understanding of SCCOHT. Two cases diagnosed with SCCOHT from our medical database were reconfirmed and immunohistochemically stained with vimentin, CK, EMA, S-100, ER, PR, and SMARCA4. Diffuse small, round cells with scant cytoplasms, small nucleoli, hyperchromatic nuclei, and active nuclear divisions were detected in the microscopy. The immunohistochemical markers indicated minor positive but notably were SMARCA4 negative, which led to the final diagnosis. SCCOHT is a rare and lethal ovarian tumor in young women. The loss of SMARCA4 or the presence of SMARCA2 is a specific marker for the disease. Susceptibility to CDK4/6 inhibitors associated with downregulation of SMARCA4 targeted cyclin D1 may be a probable therapeutical mechanism for the disease.

Sinonasalteratocarcinosarcoma: a report of two cases and clinicopathological analysis.

Sinonasalteratocarcinosarcoma (SNTCS) is a highly malignant and aggressive neoplasm which can quickly damage the local soft tissue, bone tissue, and invade orbital and intracranial tissues. It also can result in local lymph node and distant organ metastasis. The data from 2 cases of SNTCS from the First Affiliated Hospital of Bengbu Medical College (China), treated with radiotherapy and chemotherapy followed by cranio-facial resection, were analyzed since 2016. The main symptoms of the two patients were of the nasal cavity with nasal congestion and runny nose. There was no recurrence after surgery. Microscopic examination showed that the composition of tumor tissue was very complex, as different degrees of differentiation of the origin of the organization could be seen in the tumor tissue. It was mixed with teratoma and cancer sarcoma components and undifferentiated/primitive tumor cells could also be seen in local tumor stroma. SNTCS is a very rare complex tissue composition of malignant tumors, because of its complex pathological morphology and high possibility of misdiagnosis. Pathological features and immunohistochemical markers can contribute to the diagnosis and differential diagnosis of the disease.

Elevated expression of yes­associated protein is associated with the malignant status and prognosis of laryngeal squamous cell carcinoma.

Previous studies have demonstrated that elevated yes­associated protein (YAP) expression is associated with tumor aggression and poor prognosis in various types of human cancer. However, the clinicopathological significance and the prognostic value of YAP in laryngeal squamous cell carcinoma (LSCC) is unknown. The aim of the present study was to identify the expression pattern and prognostic significance of YAP in patients with LSCC. YAP mRNA and protein expression levels were examined in fresh and archived LSCC samples using the reverse transcription­quantitative polymerase chain reaction, immunohistochemistry (IHC) and western blotting. The association between YAP expression levels with the malignant status and prognosis of patients with LSCC was analyzed. Upregulated protein and mRNA expression levels of YAP were detected in LSCC tissues compared with paired healthy surgical margin tissues. Positive expression of YAP was identified in 84/121 (69.4%) LSCC tissues and in 4/30 (13.3%) healthy surgical margin tissues by IHC. Positive YAP protein expression was significantly associated with clinical stage, TNM classification, lymph node metastasis and differentiated degree. Patients with positive YAP expression exhibited a significantly decreased overall survival time compared with patients with negative YAP expression (P=0.0002). Multivariate analysis indicated that the level of YAP expression was an independent prognostic factor for poor survival in patients with LSCC (P=0.012). In conclusion, the expression level of YAP was significantly increased in LSCC and associated with the malignant status of LSCC. Therefore, YAP may represent a novel biomarker for predicting the prognosis of patients with LSCC.

Knockdown of ST6Gal-I increases cisplatin sensitivity in cervical cancer cells.

BACKGROUND: Sialyltransferase I (ST6Gal-I) is an enzyme involved in tumor metastasis that processes sialic acid precursors into their mature form, enabling them to regulate gene expression. However, the effect of ST6Gal-I on the biological behavior of cancer cells remain unclear. This study was the first to demonstrate the influence of ST6Gal-I on cisplatin sensitivity in cervical cancer cells. METHODS: Knockdown of ST6Gal-I was performed by shRNA and HeLa cells combination with cisplatin were tested. RESULTS: We showed that down-regulation of ST6Gal-I promoted cell apoptosis and inhibited proliferation and invasion in cervical cancer cells. Knockdown of ST6Gal-I by RNA interference increased the sensitivity of HeLa cells to cisplatin in vitro, and reduced tumor volume and suppressed subcutaneous tumor growth in response to cisplatin treatment in a xenograft mouse model in vivo. CONCLUSIONS: The results provide new information that ST6Gal-I plays an important role in several biological or pathological processes including drug resistance in cervical cancer and may be a potential therapeutic target to improve the response to chemotherapy in cervical cancer patients.

Clinicopathological study of centrally necrotizing carcinoma of the breast.

BACKGROUND: Centrally necrotizing carcinoma of the breast (CNC) represents a newly-identified subset of breast cancer. The clinical and pathological characteristics of this breast cancer subtype are not yet completely understood. METHODS: We assessed the clinicopathological characteristics of 73 cases of CNC and 30 control cases of high-grade infiltrating ductal carcinoma (IDC) with focal necrosis based on light microscopy and immunohistochemical staining for estrogen receptor, progesterone receptor, Cerb-B2/HER2, Ki-67, epidermal growth factor receptor, cytokeratin 5/6, smooth muscle actin, S-100 protein, p63 and CD10. RESULTS: All the tumors showed extensive central necrotic or acellular zones with different degrees of fibrotic or hyaline material surrounded by ring-like or ribbon-like residual tumour tissue which were usually high-grade IDCs. The central necrotic zone accounted for at least 30% of the cross-sectional area of the tumor. Thirty-six cases (49.3%) showed a component of ductal carcinoma in situ. The tumorous stroma around the central necrotic zone was accompanied by myxoid matrix formation in 28 cases (40%). Lymphocytic infiltration was present in 53 cases (72.6%). Granulomatous reactions were detected at the periphery of the tumors in 49 cases (67.1%). Immunohistochemistry showed greater expression of basal-like markers (72.2%, 52 cases) than myoepithelial markers (60.6%, 43 cases), both of which were significantly higher than in controls (26.7%, 8 cases) (P < 0.001). According to molecular typing, most CNCs were basal-like subtype (37 cases, 50.7%). Follow-up data were available for 28 patients. Disease progression occurred in 11 patients. The combined rate of recurrence, distant metastasis or death was significantly higher in CNC patients compared with controls (P < 0.05). CONCLUSIONS: CNC was associated with distinctive clinicopathologic features mostly characterized as basal-like type. Its high proliferative activity, highly-aggressive biological behavior, and high rates of recurrence and metastasis, suggest that CNC should be classified as a new type of breast carcinoma.

[Nodular histiocytic/mesothelial hyperplasia: a clinicopathologic analysis of 7 cases].

OBJECTIVE: To analyze the clinicopathologic and immunohistochemical features of nodular histiocytic/mesothelial hyperplasia (NHMH) and to improve the knowledge of this disease. METHODS: Seven cases of NHMH were collected and the clinicopathologic and immunohistochemical data were analyzed with review of the literature. RESULTS: Seven male patients aged from 1.5 to 5.0 years (mean 2.8). The main clinical symptom was an inguinal mass.Grossly, main pathological changes were the mural nodule or free nodule in lumen, with diameter of 0.1-0.5 cm.Histologically, the tumor cell morphology was relatively single, cohesive polygonal or oval cells which were arranged in solid sheets or nests, usually with ovoid or deeply grooved nuclei and a moderate amount of pale pink cytoplasm in the nodular collection area. The nuclei had delicate chromatin and no obvious atypia, and mitosis was incidentally found. A few scattered lymphocytes were found in the stroma. The cyst wall was lined by a single layer of mesothelial cells.Immunohistochemically, the most cells in nodular lesion were strongly positive for the histiocytic marker CD68, vimentin and α1-antichymotrypsin, while lining mesothelial cells on the wall were positive for calretinin, MC, WT1, CK5/6, CKpan and EMA. CONCLUSIONS: NHMH is a rare and benign tumor-like lesion, and easy to be misdiagnozed, which should be distinguished from neuroendocrine tumors, Langerhans cell histiocytosis, seminoma, mesothelioma and so on. The correct diagnosis of this lesion depends on the clinical characteristics, morphology and immunohistochemistry.

Aberrant expression of hypoxia-inducible factor 1α, TWIST and E-cadherin is associated with aggressive tumor phenotypes in endometrioid endometrial carcinoma.

OBJECTIVE: Intratumoral hypoxia promotes angiogenesis, invasion and epithelial-mesenchymal transition, a pivotal event in tumor metastasis. TWIST is a master regulator of multiple developmental processes and has recently been shown to be the key factor responsible for cancer metastasis via the inhibition of E-cadherin expression, a hallmark of epithelial-mesenchymal transition. This study aimed to determine the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in patients with endometrioid endometrial carcinoma and to examine their clinical significance in endometrioid endometrial carcinoma progression. METHODS: Using immunohistochemical and tissue microarray approaches, we evaluated the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in normal endometrial (n = 35), atypical hyperplasia (n = 28) and endometrioid endometrial carcinoma samples (n = 124). Furthermore, we statistically analyzed the association between these markers, as well as their correlation with clinicopathologic variables. RESULTS: The expression of hypoxia-inducible factor 1α and TWIST were markedly increased, whereas E-cadherin was decreased, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma (P < 0.01). Among various clinical parameters, the expression of hypoxia-inducible factor 1α and TWIST was strikingly elevated with aggressive tumor characteristics, including higher pathologic grade, deep myometrial invasion and lymph node involvement (P < 0.05). More importantly, overexpression of hypoxia-inducible factor 1α positively correlated with enhanced TWIST expression in endometrioid endometrial carcinoma samples (r = 0.249, P < 0.01); however, statistical analysis showed a negative relationship between TWIST upregulation and E-cadherin downregulation (r = -0.183, P = 0.042). CONCLUSIONS: These results demonstrated for the first time that the hypoxia-inducible factor 1α/TWIST/E-cadherin pathway may play a critical role in invasion and metastasis of endometrioid endometrial carcinoma. The combined evaluation of these markers may be useful in predicting aggressive phenotypes and thus prognosis in patients with endometrioid endometrial carcinoma.

Expression of PTTG1 and PTEN in endometrial carcinoma: correlation with tumorigenesis and progression.

Human pituitary tumor-transforming gene 1 (PTTG1) is a newly identified proto-oncogene, and its overexpression occurs in a wide variety of human cancers. The tumor suppressor gene phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is frequently mutated or deleted in numerous tumors, especially in endometrial carcinoma. The aim of this study was to investigate whether the aberrant expression of PTTG1 and PTEN is associated with tumorigenesis and progression of endometrial carcinoma. Tissue microarray and immunohistochemical staining were undertaken in 124 endometrial carcinoma, 28 atypical hyperplasia and 35 normal endometrium samples. Then, the correlation of PTTG1 and PTEN expression with the clinicopathological features and with the levels of estrogen and progesterone receptor was analyzed. The presence of PTTG1 and PTEN protein was significantly increased and decreased, respectively, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma. PTTG1 protein showed a significantly positive correlation with TNM stage, but not with other characteristics. In addition, PTEN protein did not correlate with any parameters except for histological grade, to which it was found to be inversely related. Statistical analysis confirmed a significant relationship between an increase in PTTG1 and a decrease in PTEN. These results indicate that high expression of PTTG1 and low expression of PTEN may be involved in pathogenesis and development of endometrial carcinoma. The findings also provide evidence that combined evaluation of the two markers may be useful in predicting tumor behavior and thus prognosis.

[Clinicopathologic analysis of the nipple-areolar complex occult involvement in early stage breast carcinoma].

OBJECTIVE: The aim of this study was to investigate the incidence of nipple-areola complex (NAG) involvement in stage I - II a breast cancer patients who underwent skin-sparing mastectomy and to determine the associated risk factors, to provide a theoretical basis for modified radical mastectomy preserving NAC and breast reconstruction in early stage breast cancer patients. METHODS: A total of 68 women with primary breast cancer were included in this study. The following associated risk factors of NAC involvement were assessed and compared with those of non-involvement: the distance from the tumor site to the edge of areola (D), axillary lymph node status, over-expression of HER-2/neu, location of tumor, TNM stage, abnormal nipple (nipple indentation, erosion, discharge), tumor size, age, histological type, as well as status of estrogen receptor (ER) and progesterone receptor (PR), by Chi-square test. RESULTS: The positive rate of NAG involvement was 13.2%. It decreased with an increase in the distance from the tumor site to the edge of the areola (D) (chi2 = 10.68, P <0.01)), and higher incidence of NAG involvement was found in patients with axillary lymph node metastasis (chi2 = 14. 61, P < 0.01) and over-expression of HER-2/neu (chi2 =6.83, P <0.01). Location of tumor (P <0.01), TNM stage (chi2 =3.85, P <0.05), abnormal nipple (chi2 = 11.65, P<0.01), and tumor size (chi2 =4.13, P <0.05) also had influence on the NAG involvement. No significant correlation between NAC involvement and age (P > 0.05)), histological type (chi2 = 0.07, P > 0.05)), as well as status of estrogen receptor (ER) (chi2 = 0.06, P > 0.05) and progesterone receptor (PR) (chi2 = 0.04, P > 0.05) was found. Most of the NAG involvement was caused by ductal infiltration. CONCLUSION: In the stage I - II a breast cancer patients, location of tumor, TNM stage, the distance from the tumor site to the edge of areola (D), abnormal nipple, over-expression of HER-2 and metastases in axillary lymph nodes are the primary influential factors of NAG involvement.