BACKGROUND/AIMS: Lysyl oxidase-like 2 (LOXL2), a collagen-modifying enzyme, has been implicated in cancer invasiveness and metastasis. METHODS: We evaluated the expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin 19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected hepatocellular carcinomas (HCCs) by immunohistochemistry. RESULTS: LOXL2 positivity was found in 14.3% (15/105) of HCCs, and it was significantly associated with high serum α-fetoprotein levels, poor differentiation, fibrous stroma, portal vein invasion, and advanced TNM stage (p < 0.05 for all). Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005) and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be an independent predictor of overall survival and disease-specific survival (p < 0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an independent predictor for overall survival, disease-specific survival, disease-free survival, and extrahepatic recurrence-free survival (p < 0.05 for all). CONCLUSIONS: LOXL2 expression represents a subgroup of HCCs with more aggressive behavior and is suggested to be a poor prognostic marker in HCC patients.
Carbonic Anhydrases ; Carcinoma, Hepatocellular* ; Disease-Free Survival ; Epithelial Cells ; Extracellular Matrix ; Humans ; Immunohistochemistry ; Interleukin-6 ; Keratin-19 ; Neoplasm Metastasis ; Portal Vein ; Prognosis*

Psoriasis is an auto-immune skin disease, which is characterized by the excessive generation of plaques on the skin with typically a long-lasting red, itchy and scaly symptoms. Imiquimod, which has been used for the treatment of external genital warts, actinic keratosis, and superficial basal cell carcinoma, induced of psoriasis-like skin disorders with skin erythema and thickness in mice. In the present study, we tried to find the bioactive herbal extract against imiquimod-induced psoriasis-like skin disorder in mice. During the searching of the herbal extract with anti-psoriatic effect, the ethanolic extract of Cnidium officinale ameliorated imiquimodinduced psoriasis-like skin disorder in mice. The morphological evaluation, H&E staining and Psoriasis Area and Severity Index (PASI) score showed that ear and back thickness, and erythema induced by imiquimod were significantly reversed after the treatment of the cream of the ethanolic extract of C. officinale. The overexpressed myeloperoxidase (MPO) and keratin 6A levels were decreased by the treatment of C. officinale cream. Also, IFN-γ, c-fos and IκB-α mRNA levels, which are related to the progression of psoriasis, were reduced by C. officinale cream. Thus, the ethanolic extract of C. officinale ameliorated psoriasis-like skin disorder induced by imiquimod and might be the therapeutic agent for psoriasis.
Animals ; Carcinoma, Basal Cell ; Cnidium ; Condylomata Acuminata ; Ear ; Erythema ; Ethanol ; Keratin-6 ; Keratosis, Actinic ; Mice ; Peroxidase ; Psoriasis ; RNA, Messenger ; Skin Diseases ; Skin

Both mature and stem cell-derived hepatocytes lost their phenotype and functionality under conventional culture conditions. However, the 3D scaffolds containing the main extracellular matrix constitutions, such as heparin, may provide appropriate microenvironment for hepatocytes to be functional. The current study aimed to investigate the efficacy of the differentiation capability of hepatocytes derived from human Wharton's jelly mesenchymal stem cells (WJ-MSCs) in 3D heparinized scaffold. In this case, the human WJ-MSCs were cultured on the heparinized and non-heparinized 2D collagen gels or within 3D scaffolds in the presence of hepatogenic medium. Immunostaining was performed for anti-alpha fetoprotein, cytokeratin-18 and -19 antibodies. RT-PCR was performed for detection of hepatic nuclear factor-4 (HNF-4), albumin, cytokeratin-18 and -19, glucose-6-phosphatase (G6P), c-met and Cyp2B. The results indicated that hepatogenic media induced the cells to express early liver-specific markers including HNF4, albumin, cytokeratin-18 and 19 in all conditions. The cells cultured on both heparinized culture conditions expressed late liver-specific markers such as G6P and Cyp2B as well. Besides, the hepatocytes differentiated in 3D heparinized scaffolds stored more glycogen that indicated they were more functional. Non-heparinized 2D gel was the superior condition for cholangiocyte differentiation as indicated by higher levels of cytokeratin 19 expression. In conclusion, the heparinized 3D scaffolds provided a microenvironment to mimic Disse space. Therefore, 3D heparinized collagen scaffold can be suggested as a good vehicle for hepatocyte differentiation.
Antibodies ; Collagen ; Collagen Type I ; Constitution and Bylaws ; Extracellular Matrix ; Fetal Proteins ; Gels ; Glucose-6-Phosphatase ; Glycogen ; Heparin ; Hepatocytes* ; Humans ; Keratin-18 ; Keratin-19 ; Mesenchymal Stromal Cells* ; Phenotype ; Wharton Jelly

OBJECTIVETo investigate the expression of p16INK4a protein in breast cancer and analyze its clinical significance.

METHODSA total of 132 surgical specimens of primary breast cancer obtained between 2014 and 2015 were examined for expressions of ER, PR, CK5/6, Her-2 and p16INK4a proteins using immunohistochemistry.

RESULTSThe breast cancer samples were classified into 5 molecular subtypes, namely Luminal A (58 cases), Luminal B (32 cases), Her-2-positive (21 cases), basal-like (12 cases) and normal-like (9 cases) types. p16INK4a expression was negative in 7/132 (5.30%) cases, weakly positive in 15/132 (11.36%) cases, positive in 40/132 (30.30%) cases, and strongly positive in 70/132 (53.03%) cases. When categorizing negative and weakly positive cases into negative group and the positive and strongly positive cases into positive group, the total negative and positive expression rates of p16INK4a were 16.67% (22/132) and 83.33% (110/132) in the carcinoma tissues. Statistical analysis showed the expression intensity of p16INK4a differed significantly between the age groups (P<0.05) but was not significantly correlated with ER, PR, Her-2, molecular subtypes or metastasis of the tumors.

CONCLUSIONThe compensatory high expression of p16INK4a is the main mechanism of cell cycle deregulation in invasive breast cancer and can be an important specific molecular marker for invasive breast cancer.

Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; classification ; diagnosis ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Humans ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC).

METHODSImmunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC. The diagnostic value of these markers was evaluated.

RESULTSThe expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied. Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity (P < 0.01). On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8% (170/275), 85.5% (242/283) and 89.2% (248/278), respectively. The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 (P < 0.01). TTF1 was expressed in 77.2% (217/281).

CONCLUSIONSp63 and p40 are expressed in a subset of SCLC. In contrast, CK5/6 is rarely positive in SCLC. An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.

CD56 Antigen ; genetics ; metabolism ; Chromogranin A ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Diagnosis, Differential ; Humans ; Keratin-5 ; genetics ; metabolism ; Keratin-6 ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; Small Cell Lung Carcinoma ; genetics ; metabolism ; Synaptophysin ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) .

METHODSThe clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry.

RESULTSPositive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH.

CONCLUSIONIn the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS.

Breast ; metabolism ; pathology ; Breast Neoplasms ; diagnosis ; metabolism ; Carcinoma, Ductal, Breast ; diagnosis ; metabolism ; Carcinoma, Intraductal, Noninfiltrating ; diagnosis ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; diagnosis ; metabolism ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast.

METHODSClinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed.

RESULTSAll six patients were female, age ranged from 37 to 71 years (average 49.3 years). Three cases were cystic hypersecretory hyperplasia (CHH), the other three cases were cystic hypersecretory carcinoma (CHC). Clinically the lesions presented as either breast mass or mammographic calcification.Grossly, the cystic hypersecretory lesions were poorly circumscribed, with multiple colloid containing cysts on the cut surface. Microscopically, the remarkable feature was numerous enlarged cysts which contained densely eosinophilic homogeneous secretion similar to the colloid seen in thyroid follicles, and calcification was seen in the cyst in one case. The secretion was D-PAS and mucicarmine positive. The lining epithelium of the cysts was uniformly flat, cuboid or columnar, and arranged in a monolayer. The cells may be arranged in turfs, solid or micropapillary patterns in CHH.In cases with dysplasia, the epithelium showed cytological and structural atypia, but the usual morphology of atypical dutal hyperplasia such as arcades, rigid bridges or cribriform pattern was less common. The three CHC included two invasive ductal carcinomas (IDC) and one ductal carcinoma in situ (DCIS).In CHL, there was immunoreactivity to S-100 protein, CK5/6 and CK14.Of the three CHCs, ER and PR were expressed in only one IDC.No HER2 expression was identified in the two invasive CHCs.One patient was lost to follow-up, and the rest were uneventful at 18 months.

CONCLUSIONSCHL of the breast is a rare pathological entity. Multiple colloid-filled cysts is a unique histological feature. The epithelium of CHL may show usual hyperplasia, dysplasia or carcinoma.

Adult ; Aged ; Breast ; pathology ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; surgery ; Epithelium ; pathology ; Female ; Fibrocystic Breast Disease ; metabolism ; pathology ; surgery ; Humans ; Hyperplasia ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Lymphatic Metastasis ; Middle Aged ; S100 Proteins ; metabolism

OBJECTIVETo investigate the clinicopathologic features, clinical progress and prognosis of the basal-like subtype of invasive lobular carcinoma (ILC) of the breast.

METHODSFour cases of ILC were analyzed by detailed histopathologic observation and immunohistochemical staining for E-cadherin, p120 catenin, ER, PR, HER2, CK5/6, EGFR, p63, p53, Ki-67 using MaxVision method. The follow-up and clinical data were analyzed.

RESULTSMorphologically, one case was mixed ILC and three cases were pleomorphic ILC. The tumor cells were negative for E-cadherin except one case with focal membrane positivity, and all showed p120 catenin cytoplasmic positivity except one case with focal membrane positivity. All cases were negative for ER, PR and HER2 (triple negative), and positive for EGFR and CK5/6. Two cases were positive for p63. The cases were partly and weakly positive for p53, and the Ki-67 positive rate was between 30% and 75%. Follow-up data showed that two cases developed chest wall metastases, and in one case, there was progression to liver and abdominal metastases.

CONCLUSIONSILC of the breast are ER, PR and HER2 "triple negative", CK5/6 and EGFR positive, indicative of basal-like characteristics. Basal-like subtype of ILC are peculiarly prone to metastasis and poor response to chemotherapy, suggesting that it is associated with poor prognosis.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Catenins ; metabolism ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Ki-67 Antigen ; metabolism ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Thoracic Neoplasms ; secondary ; Thoracic Wall ; Tumor Suppressor Protein p53 ; metabolism

Carcinoma, Squamous Cell ; pathology ; Child ; Cysts ; pathology ; Diagnosis, Differential ; Epithelium ; pathology ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Keratin-7 ; metabolism ; Keratins ; metabolism ; Neoplasm Recurrence, Local ; surgery ; Reoperation ; Submandibular Gland ; surgery ; Submandibular Gland Neoplasms ; metabolism ; pathology ; surgery ; Transcription Factors ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; metabolism

Biopsy, Needle ; Breast ; pathology ; Breast Neoplasms ; classification ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Membrane Proteins ; metabolism ; Papilloma, Intraductal ; metabolism ; pathology ; Receptors, Estrogen ; metabolism