Clinical value of Cyclin D1 and P21 in the differential diagnosis of papillary thyroid carcinoma.

BACKGROUND: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. METHODS: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. RESULTS: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. CONCLUSIONS: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.

Arthritis of the hip caused by arteriovenous malformations: A case report.

BACKGROUND Arthritis of the hip caused by arteriovenous malformations (AVMs) has been rarely reported. Therefore, total hip replacement (THR) in patients with AVM-induced arthritis of the hip is challenging. CASE SUMMARY We report a 44-year-old woman with aggravated right hip pain during the past decade. The patient presented with severe pain and a functional disorder of the right hip. X-ray examination revealed severely narrowed right hip joint space and abnormal trabecular bone loss in the femoral neck and trochanter area. Doppler ultrasound, magnetic resonance imaging and computed tomography angiography revealed AVMs surrounding the right hip, along with erosion. To ensure the safety of THR, we performed vascular embolization and temporary balloon occlusion of the iliac artery three times during the operation. However, serious hemorrhage occurred, which was rescued by the multimodality blood conservation strategy. THR was successfully performed, and the patient was discharged 8 d later for rehabilitation. Postoperative pathological examination showed osteonecrosis of the femoral head with malformed thick-walled vessels and focal granulomatous inflammation of the surrounding soft tissues. The Harris Hip Scale score increased from 31 to 82 at 3 mo of follow-up. The patient was followed up for 1 year, and all her clinical symptoms were significantly alleviated. CONCLUSION Arthritis of the hip caused by AVMs is rare in clinical practice. The activity and function of the involved hip joint can be effectively treated with THR after comprehensive imaging and multidisciplinary consultation.

Familial gastrointestinal stromal tumors with KIT germline mutation in a Chinese family: A case report.

BACKGROUND: Familial gastrointestinal stromal tumors (GISTs) is a rare autosomal dominant disorder characterized by an array of clinical manifestations. Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far. It is often characterized by a series of manifestations, such as multiple lesions and hyperpigmentation. However, the effect of imatinib treatment in these patients is still uncertain. CASE SUMMARY: Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 (p.V560G) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient. CONCLUSION: Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.

Heel pain caused by os subcalcis: A case report.

BACKGROUND: The accessory bones are common bone variations around the feet and ankles, which usually originate from nonunion of the secondary ossification center adjacent to the main bone mass, and most of them remain asymptomatic. Os subcalcis is an accessory bone at the plantar aspect of the calcaneus, which is located just posterior to the insertion of the plantar fascia. Focal bone formation at the calcaneal plantar pole with heel pain has rarely been reported. CASE SUMMARY: A 55-year-old man presented to our clinic with left plantar heel pain and a progressive swelling for 8 years. X-ray, computer tomography and magnetic resonance imaging showed a large os subcalcison the plantar side of the calcaneus, located at the insertion of the plantar fascia. He underwent surgical excision of the lesion. Microscopically the bony trabeculae were intermingled with fat and covered with cartilage. CONCLUSION: This is a rare case with accessory os subcalcis leading to heel pain. It highlights the awareness of os subcalcis and helps avoid future misdiagnosis of heel pain.

Malignant Ciliated Muconodular Papillary Tumors of the Lung: A Case Report.

Ciliated muconodular papillary tumors (CMPTs) are rare peripheral lung lesions, characterized by papillary architecture and ciliated columnar cells admixed with mucous cells and basal cells. Only about 50 cases have been reported to date and is categorized as a benign neoplasm. In this article, we report an extremely rare case of 79-year-old man with a CMPT that developed in his right upper lobe. The central region of the tumor showed features of classic CMPT, while marginal area of the tumor showed the characteristics of invasive lung cancer. In central classic CMPT region, the ciliated, basal, and mucous cells were positive for thyroid transcription factor-1, cytokeratin 7 (CK7), and NapsinA. Basal cells were positive for CK5/6 and p40. Mucous cells were weakly positive for MUC2 and MUC5AC. However, CK5/6 and p40 were negative in the peripheral malignant area. Both of the benign and malignant regions had an EGFR driver mutation in exon 21. We concluded that this tumor was an extremely rare malignant case of CMPT.

MYC/BCL2 Co-Expression Is a Stronger Prognostic Factor Compared With the Cell-of-Origin Classification in Primary CNS DLBCL.

Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a subtype of DLBCL with an unfavorable prognosis and a poor response to the treatment. As we know, DLBCL is stratified into germinal center B-cell (GCB)-like and activated B-cell (ABC)-like subtypes with different prognosis according to their gene-expression characteristics. In this study, we analyzed a case series of 77 patients with primary CNS DLBCL. A difference in prognosis of GCB-like and ABC-like subtypes was noticed, but no statistical significance was found. However, significant prognostic value of MYC/BCL2 co-expression was shown. The cases with MYC/BCL2 co-expression did not show any predominance of the 2 subtypes in our cases. Furthermore, patients with MYC/BCL2 co-expression had significantly worse overall survival for both cell of origin (COO) subtypes. We conjecture that MYC/BCL2 co-expression is associated with a poorer prognosis and is independent of COO classification. Moreover, the data suggest that MYC/BCL2 co-expression is superior to COO classification assessed by immunohistochemical analysis in patients with primary CNS DLBCL.

Extended immunologic and genetic lineage of mammary analogue secretory carcinoma of salivary glands.

Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. To explore a more practical and convenient immunohistochemical approach to distinguish MASC from other tumors arising from salivary glands as well as to expand the immunologic and genetic lineage of MASC, we examined 17 MASCs using clinicopathologic, immunohistochemical, and molecular analyses. Eighteen cases of acinic cell carcinoma, 18 cases of adenoid cystic carcinoma, 22 cases of mucoepidermoid carcinoma, and 14 cases of basal cell adenocarcinoma were brought in for comparison. Seventeen MASCs shared similar architectures with not only intraluminal or intracellular secretion but also low-grade vesicular nuclei. In addition, they were all immunoreactive for S-100 and SOX-10, whereas only 3 of 17 demonstrated reactivity for GATA-3 and P63, and 4 of 17 were focally positive for CD117. ETV6 translocation was detected in 10 cases by fluorescence in situ hybridization, whereas intact ETV6 was noted in 2 cases. Our data proposed a combined immunohistochemical panel to distinguish MASC from other tumors arising from salivary glands and expanded the immunologic and genetic lineage of MASC.

Xp11 neoplasm with melanocytic differentiation of the prostate harbouring the novel NONO-TFE3 gene fusion: report of a unique case expanding the gene fusion spectrum.

Recently, an increasing number of TFE3 rearrangement-associated tumours have been reported, such as TFE3 rearrangement-associated perivascular epithelioid cell tumours (PEComas), melanotic Xp11 translocation renal cancers and melanotic Xp11 neoplasms. We have suggested that these tumours belong to a single clinicopathological spectrum. 'Xp11 neoplasm with melanocytic differentiation' or 'melanotic Xp11 neoplasm' have been proposed to designate this unique neoplasm. Herein, we describe the first case of an Xp11 neoplasm with melanocytic differentiation to be described in the prostate, bearing the novel NONO-TFE3 gene fusion. This study both adds to the spectrum regarding melanotic Xp11 neoplasms and expands its gene fusion spectrum. Moreover, we discuss the relationship of these rare tumours to neoplasms such as conventional PEComas, alveolar soft part sarcomas, malignant melanomas, clear cell sarcomas and Xp11 translocation renal cancers.

SATB1 expression is correlated with ß-catenin associated epithelial-mesenchymal transition in colorectal cancer.

SATB1, a global gene regulator, has been implicated in the growth and metastasis of multiple cancers, including colorectal cancer. While the understanding about the role of SATB1 in CRC remains limited. The aim of our study is to investigate the expression of SATB1 in CRC, and the relationship between SATB1 expression pattern and clinicopathological variables. A further aim is to analyze the correlation between SATB1 expression and epithelial-mesenchymal transition in CRC. Immunohistochemical expression of SATB1, ß-catenin, E-cadherin, CK20, Vimentin, SMA, and desmin were assessed in a cohort of 200 patients using tissue microarrays. SATB1 was expressed in 133 (66.5%) CRC primary lesions, 14 (28%) adjacent colorectal mucosa specimens, and 60 (75%) corresponding lymph node metastases. The expression level of SATB1 was significantly higher in lymph node metastases than in CRC primary lesions and normal mucosa (P = 0.000). High expression of SATB1 in CRC was strongly correlated with poor differentiation of tumor tissues (P = 0.000). High expression of SATB1 was significantly correlated with aberrant expression of ß-catenin (P = 0.0005), low expression of E-cadherin (P = 0.000) and CK20 (P = 0.000) and with high expression of Vimentin (P = 0.001). No SMA or desmin protein was expressed in the CRC cells. Our results suggested that high expression of SATB1 is significantly correlated with poor differentiation of CRC. SATB1 might promote the epithelial-mesenchymal transition by increasing the aberrant expression of ß-catenin.

Tissue inhibitor of metalloproteinase-1 protects MCF-7 breast cancer cells from paclitaxel-induced apoptosis by decreasing the stability of cyclin B1.

Paclitaxel (PTX) is a very effective drug in treating tumors. It disturbs microtubule dynamics and impairs the transition of cells from metaphase to anaphase in mitosis, leading to cell death by apoptosis. However, the effectiveness of PTX in cancer chemotherapy is hampered by drug resistance in some patients. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is well known to be capable of inhibiting apoptosis. Elevated tumor tissue TIMP-1 levels have been significantly associated with a poor response to chemotherapy. We hypothesized that TIMP-1 could reduce the sensitivity of breast cancer cells to PTX by inhibiting apoptosis. To test this hypothesis, we first examined the effects of TIMP-1 on the apoptosis induced by PTX and investigated the effects of TIMP-1 on the expression and stability of cyclin B1 that critically regulates the metaphase to anaphase transition during mitosis in MCF-7 breast cancer cells. Our data demonstrate that TIMP-1 could significantly decrease the sensitivity of MCF-7 cells to PTX-induced apoptosis, attenuate mitotic blockage in G(2)/M, and enhance the degradation of cyclin B1. To further investigate whether the inhibitory effect of TIMP-1 on PTX-induced apoptosis is mediated by lowering levels of cyclin B1, a cyclin B1-expression plasmid was transfected into clone overexpressing TIMP-1. The levels of PTX-induced apoptosis were then analyzed. The data showed that the TIMP-1-based decrease in PTX-induced apoptosis was reversed by cyclin B1. Our data indicate that TIMP-1 can protect breast cancer cells from PTX-induced apoptosis by decreasing the stability of cyclin B1.

[Troglitazone sensitizes effect of epirubicin on breast cancer cells].

BACKGROUND & OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to be highly expressed in breast cancer tissues. Thiazolidinediones (TZD), the specific ligands for PPARgamma, can inhibit cell proliferation and induce apoptosis. This study was to investigate the possibility of using troglitazone, one of TZD, as the sensitizer of epirubicin in the treatment of estrogen receptor (ER) negative breast cancer. METHODS: MTT assay and flow cytometry were used to examine the cell proliferation and apoptosis in two ER negative breast cancer cell line MDA-MB-435S and MDA-MB-231. Cells were treated with either troglitazone or epirubicin alone or co-treated with troglitazone and epirubicin. Western blot analysis was used to assess the expression level of Bcl-2. The migration potential of cells with different treatments was analyzed by the wound healing assay. RESULTS: The effect of epirubicin on inhibiting cell proliferation of breast cancer cells was enhanced by co-treatment with troglitazone in the range of 4 micromol/L to 24 micromol/L. The 50% inhibitory concentration (IC(50)) of epirubicin was reduced to 60% when combined with troglitazone compared to the treatment with epirubicin only. Treatment of cells with troglitazone or epirubicin alone could not induce significant apoptosis. However, the apoptotic indexes of MDA-MB-435S and MDA-MB-231 cells co-treated with troglitazone and epirubicin were (5.48+/-0.45)% and (10.08+/-1.89)%, respectively. Co-treatment with troglitazone and epirubicin further downregulated the expression level of Bcl-2 and inhibited cell migration simultaneously. CONCLUSIONS: Troglitazone could not only augment the effect of epirubicin on inhibiting cell proliferation and inducing apoptosis, but also suppress the migration of breast cancer cells. Troglitazone may sensitize the effect of epirubicin on breast cancer cells.