Expressions of cytokeratin 14 and proliferating cell nuclear antigen in the Hertwig's epithelial root sheath of a Vps4b knockout mouse / 华西口腔医学杂志

OBJECTIVES@#The effect of Vps4b gene mutation on the expressions of cytokeratin 14 (CK14) and proliferating cell nuclear antigen (PCNA) in the Hertwig's epithelial root sheath (HERS) is investigated.@*METHODS@#The bilateral mandibular tissues of mouse on postnatal days 5, 9, 11, 15, and 19 were removed. The mandibular first molar tissue sections were obtained after paraffin embedding. The CK14 and PCNA expressions in the epithelial root sheath of the normal mouse and Vps4b knockout mouse were compared through immunohistochemistry.@*RESULTS@#On postnatal day 5, the normal mouse began to form HERS and had a strong positive PCNA expression in the HERS cells; on postnatal day 9, the HERS structure was continuous, and PCNA was positive in the HERS cells; on postnatal day 11, a small portion of HERS began to break, and PCNA was weakly positive in the HERS cells; on postnatal day 15, HERS continued to fracture; PCNA was weakly and positively expressed in the HERS cells on the root surface; on postnatal day 19, the tooth root reached normal physiological length, and PCNA was positively expressed in the HERS cells of the terminal part. Similar to the normal mouse, the gene knockout mouse also formed a HERS structure on postnatal day 5. However, HERS began to break on postnatal day 9. On postnatal day 19, only a few fragments of HERS were found on the root surface, and the root development was immature. Moreover, the expression intensity of PCNA in the gene knockout mouse was decreased.@*CONCLUSIONS@#The Vps4b gene mutation may change the CK14 and PCNA expressions, leading to abnormal root development.

Establishment of Immortalized Primary Human Foreskin Keratinocytes and Their Application to Toxicity Assessment and Three Dimensional Skin Culture Construction

In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced blockage of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs. We also observed their robust responsiveness to various exogenous stimuli, which was evidenced by increased mRNA expression of epithelial differentiation markers and pro-inflammatory genes in response to three reactive chemicals. In addition, their applicability to cytotoxicity assessment turned out to be comparable to that of HaCaT cells. Finally, we confirmed their differentiation capacity by construction of well-stratified three dimensional skin cultures. These newly established immortalized HFKs will be valuable tools not only for generation of in vitro skin disease models but also for prediction of potential toxicities of various cosmetic chemicals.

Study of a family with epidermolysis bullosa simplex resulting from a novel mutation of KRT14 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the molecular etiology for a Chinese pedigree affected with epidermolysis bullosa simplex (EBS).</p><p><b>METHODS</b>Target region sequencing using a hereditary epidermolysis bullosa capture array combined with Sanger sequencing and bioinformatics analysis were used. Mutation taster, PolyPhen-2, Provean, and SIFT software and NCBI online were employed to assess the pathogenicity and conservation of detected mutations. One hundred healthy unrelated individuals were used as controls.</p><p><b>RESULTS</b>Target region sequencing showed that the proband has carried a unreported heterozygous c.1234A>G (p.Ile412Val) mutation of the KRT14 gene, which was confirmed by Sanger sequencing in other 8 affected individuals but not among healthy members of the pedigree. Bioinformatics analysis indicated that the mutation is highly pathogenic. Remarkably, 3 members of the family (2 affected and 1 unaffected) have carried a heterozygous c.1237G>A (p.Ala413Thr) mutation of the KRT14 gene, which was collected in Human Gene Mutation Database (HGMD). Bioinformatics analysis indicated that the mutation may not be pathogenic. Both mutations were not detected among the 100 healthy controls.</p><p><b>CONCLUSION</b>The novel c.1234A>G(p.Ile412Val) mutation of the KRT14 gene is probably responsible for the disease, while c.1237G>A (p.Ala413Thr) mutation of KRT14 gene may be a polymorphism. Compared with Sanger sequencing, target region capture sequencing is more efficient and can significantly reduce the cost of genetic testing for EBS.</p>

Nfic regulates tooth root patterning and growth / 대한해부학회지

Molecular interactions between epithelium and mesenchyme are important for root formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of root formation. However, the mechanisms of root formation and their interactions between Hertwig's epithelial root sheath (HERS) and mesenchyme remain unclear. In this study, we investigated the role of Nfic in root patterning and growth during molar root development. The molars of Nfic knockout mice exhibited an enlarged pulp chamber and apical displacement of the pulpal floor, characteristic features of taurodontism, due to delayed furcation formation. In developing molar roots of mutant mice at P14, BrdU positive cells decreased in the apical mesenchyme of the elongation region whereas those cells increased in the dental papilla of the furcation region. Whereas cytokeratin 14 and laminin were localized in HERS cells of mutant molars, Smoothened (Smo) and Gli1 were downregulated in preodontoblasts. In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars. These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner. From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

Value of CK5/6, CK14, ER and PR detection in differential diagnosis of intraductal proliferative lesions of the breast / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To 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) .</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Positive 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.</p><p><b>CONCLUSION</b>In 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.</p>

Weber-Cockayne Type Epidermolysis Bullosa Simplex Resulting from a Novel Mutation (c. 608T>C) in the Keratin 5 Gene

Epidermolysis bullosa simplex (EBS), an inherited genetic disorder, is most often caused by a dominant-negative mutation in either the keratin 5 (KRT5) or the keratin 14 (KRT14) gene. These keratin mutants result in a weakened cytoskeleton and cause extensive cytolysis. It is important to analyze the KRT5 or KRT14 genes of the patient and their family members by mutational analysis in order to identify genetic defects as well as the need for genetic counseling. In this study, we present a 5-year-old Korean boy who had been developing blisters and erosions on the palms of his hands and soles of his feet since infancy. In addition, while his younger sister and father showed similar clinical manifestation, his mother did not. The patient was diagnosed with EBS based on clinical manifestation, which is characterized by the presence of blisters restricted to the palms and soles, histological findings, and mutational analysis. Mutational analysis of the patient's DNA revealed a thymine-to-cytosine transition at codon 608 in the KRT-5 gene, resulting in a leucine-to-proline substitution in the keratin 5 protein. The same mutation was identified in the paternal, but not maternal, DNA. Here, we report a case of Weber-Cockayne type EBS with vesicles and bullae restricted to the palms and soles with a novel, paternally inherited mutation in KRT5 gene (exon2, c.608T>C).

Clinicopathologic features of cystic hypersecretory lesion of the breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast.</p><p><b>METHODS</b>Clinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed.</p><p><b>RESULTS</b>All 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.</p><p><b>CONCLUSIONS</b>CHL 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.</p>

Heterogeneity of glandular cells in the human salivary glands: an immunohistochemical study using elderly adult and fetal specimens / 대한해부학회지

Using immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.

Clinicopathologic features and immunohistochemistry of the basal-like subtype of invasive breast carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features and immunohistochemical of the basal-like subtype of invasive breast carcinoma (BLBC), and to discuss the diagnosis standard.</p><p><b>METHODS</b>Immunohistochemistry was performed in 448 cases of breast carcinoma and these cases were categorized into luminal A, luminal B, null subtypes, HER2-overexpressing and basal-like and their clinicopathologic features were observed under light microscope with stains of HE and immunohistochemical InVitrogen staining.</p><p><b>RESULTS</b>Among the breast cancer patients, the incidence of BLBC was 15.4% (69/448). Morphologic features significantly associated with BLBC constituently included nest structure and showing diffuse growth pattern, large scarring areas without cells in tumor, geographic necrosis, pushing margin of invasion, lymphocytic infiltrate in various degree in tumor stroma, syncytial tumor cell without clear boundaries, tumor cell showing vesicular unclear chromatin and nucleolus, markedly elevated mitotic count, metaplasia (all P < 0.01). Meanwhile, most BLBC showed strong immunoreactivity for CK5/6, CK14, CK17 (all P < 0.01).</p><p><b>CONCLUSION</b>BLBC showed distinct morphologic and immunophenotypic features.</p>

Mechanism of psoriasis generation in animal models / 药学学报

Psoriasis is a chronic inflammatory disease related to genome-wide and surroundings, it is important to develop a suitable animal model to research psoriasis pathogenesis and evolve pharmacotherapeutics. With the development of transgenetic technology in the past few years, psoriasis virulence gene animal model become a hotspot. Research of animal model of human psoriasis genes is reviewed in the paper.

Evaluation of Bronchiolar and Alveolar Cell Injuries Induced by Short- and Long-term Exposure to Sidestream Smoke

BACKGROUND: We investigated effects of short- and long-term exposure to sidestream smoke on the bronchiolar and alveolar cells in Sprague-Dawley rats. METHODS: Rats were divided into five experimental groups: groups 1, 2, and 3 (1-month exposure to 3, 5, and 7 cigarettes a day, respectively), groups 4 and 5 (3- and 6 month exposure to five cigarettes a day, respectively). We examined the morphologic changes, the expressions of tumor necrosis factor alpha (TNF-alpha), tumor growth factor beta1 (TGF-beta1), interlekin (IL)-1alpha, IL-1beta, Ki-67, and cytokeratin 14 and in situ apoptosis in the bronchiolar and alveolar cells on light microscopy (LM) and electron microscopic (EM) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: LM showed the respiratory bronchiolar dilatation and alveolar wall collapse. In groups 3, 4, and 5, EM showed loss of the cilia and Clara cells with irregular size, more prominent alveolar wall collapse and dilation of alveolar duct than those of groups 1 and 2. Bronchiolar and alveolar cells showed increased expressions of TNF-alpha and TGF-beta in groups 4 and 5. LM and EM TUNEL stains showed increased apoptosis in groups 3, 4, and 5. CONCLUSIONS: Sidestream smoke causes a bronchiolar and alveolar cell injury and the severity correlates strongly the volume and duration of exposure to sidestream smoke.

Solid variant of mammary adenoid cystic carcinoma with basaloid features: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic and immunohistochemical features as well as the differential diagnoses of the solid variant of mammary adenoid cystic carcinoma with basaloid features.</p><p><b>METHODS</b>Clinical and pathological data were collected in four cases of the solid variant of mammary adenoid cystic carcinoma with basaloid features, and microscopic pathological examination and immunohistochemistry EnVision method were performed. The relevant literature was also reviewed.</p><p><b>RESULTS</b>The four patients were female, with age ranged from 46 - 65 years old (average 56 years) and the maximum tumor diameter ranged from 1.5 to 2.5 cm. Microscopically, the tumors exhibited a predominantly solid architecture with a myxoid or hyalinized stroma. The tumor cells showed moderate to marked nuclear atypia, and a basaloid appearance with scanty cytoplasm and inconspicuous nucleoli, and ≥ 5 mitotic figures per 10 high power fields. Glandular space embedded within tumor islands could be noticed. These spaces were genuine glandular structures and the cells lining these true glandular lumens had more abundant and eosinophilic cytoplasm. Pseudoglandular spaces of cribriform pattern or variable shape were also occasionally seen, and these cysts contained homogenous eosinophilic material. Focal necrosis was found. All cases were negative for ER, PR and HER2. Immunohistochemical staining for CK5/6, CK7 and CK14 was positive in the genuine glandular structures. All cases were positive for CD10, but also positive with varying intensity from weak to strong for vimentin and CD117. Staining for Ki-67 in three patients showed 10% - 50% positive.</p><p><b>CONCLUSIONS</b>The solid variant of mammary adenoid cystic carcinoma with basaloid features is a histologically distinctive and also a rare subset of the mammary adenoid cystic carcinoma. Awareness of its pathological features can help with the diagnosis as well as differential diagnosis. More cases are still needed for accurately assessing the prognosis of this particular tumor.</p>

The Epithelial-Mesenchymal Transition During Tooth Root Development

Hertwig's epithelial root sheath (HERS) consists of bilayered cells derived from the inner and outer dental epithelia and plays important roles in tooth root formation as well as in the maintenance and regeneration of periodontal tissues. With regards to the fate of HERS, and although previous reports have suggested that this entails the formation of epithelial rests of Malassez, apoptosis or an epithelialmesenchymal transformation (EMT), it is unclear what changes occur in the epithelial cells in this structure. This study examined whether HERS cells undergo EMT using a keratin-14 (K14) cre:ROSA 26 transgenic reporter mouse. The K14 transgene is expressed by many epithelial tissues, including the oral epithelium and the enamel organ. A distinct K14 expression pattern was found in the continuous HERS bi-layer and the epithelial diaphragm were visualized by detecting the beta-galactosidase (lacZ) activity in 1 week postnatal mice. The 2 and 4 week old mice showed a fragmented HERS with cell aggregation along the root surface. However, some of the lacZ-positive dissociated cells along the root surface were not positive for pan-cytokeratin. These results suggest that the K14 transgene is a valuable marker of HERS. In addition, the current data suggest that some of the HERS cells may lose their epithelial properties after fragmentation and subsequently undergo EMT.

Clinicopathologic and immunohistochemical study of 187 cases of intraductal papillary neoplasm of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the diagnostic approach and criteria for intraductal papillary neoplasms of breast.</p><p><b>METHODS</b>According to the criteria of 2003 WHO classification, 187 cases of intraductal papillary neoplasm of breast were identified and enrolled into the study. The clinical and histologic features were reviewed and immunohistochemical study for CD10, p63, CK14, CK5/6, CK7, MGB1 and p53 were carried out on 53 cases.</p><p><b>RESULTS</b>Amongst the 187 cases studied, there were 128 cases of intraductal papilloma, 16 cases of atypical intraductal papilloma and 43 cases of intraductal papillary carcinoma. They showed a spectrum of morphologic features including epithelial and stromal hyperplasia and secondary changes. The expression of myoepithelial markers, including CD10 and p63, significantly decreased in ascending order from intraductal papillomas, atypical intraductal papillomas and intraductal papillary carcinomas (P < 0.001). The expression of basal cell markers, including CK5/6 and CK14, showed a mosaic pattern in benign lesions and significantly decreased or was absent in atypical and carcinomatous lesions (P < 0.001). In contrast, the luminal cell marker CK7 expressed in the three groups with no statistically significant difference (P = 0.06). On the other hand, the expression of MGB1 in intraductal papillary carcinomas was much lower than that in the other two groups (P = 0.002 and P = 0.007). The staining for p53 was negative in all of the three groups.</p><p><b>CONCLUSIONS</b>Intraductal papillary neoplasms of breast represent a heterogeneous group of lesions with various morphologic appearances. Correlation with immunostaining results for myoepithelial markers, basal-type cytokeratins and luminal epithelial markers are helpful in arriving at a definitive diagnosis.</p>

Mutation analysis of keratin 5 and keratin 14 genes in a family with epidermolysis bullosa simplex with mottled pigmentation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples obtained from eleven patients from the family and controls. All the exons of K5 and K14 genes were amplified using polymerase chain reaction (PCR) and directly sequenced.</p><p><b>RESULTS</b>By DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was detected. The same mutation was not found in non-affected members from the family and normal controls.</p><p><b>CONCLUSION</b>Mutation in K5 gene (c.237C>T) may be responsible for the development of disease in this family.</p>

The Keratin-14 Expression in Actinic Keratosis and Squamous Cell Carcinoma: Is This a Prognostic Factor for Tumor Progression? / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Actinic keratosis (AK) is an incipient form of cutaneous squamous cell carcinoma (SCC). We determined if the pattern of expression of keratin-14 (K14) is a factor for tumor progression in AK and SCC. MATERIALS AND METHODS: Eighteen sections from the tissues of 16 patients were stained with anti-K14 antibody and p16(INK4a). Among the 16 patients, 4 were diagnosed with both SCC and AK at the same site, but AK developed first and SCC developed subsequently. Thus, SCC may have evolved from AK. The other 12 patients were only diagnosed with AK. RESULTS: In all of the AK and SCC tissues, basement membranes showed positive staining for K14. However, strong reactivities were shown in the spinous and granular layers and focuses of dermal invasion in the SCC tissues developed from AK. Two and 3 of the 12 AK cases had moderately positive reactions for K14 in the spinous and granular layers, respectively. Also, all SCC tissues except one had moderate-to-strong reactions in the basal, spinous, and granular layers for p16(INK4a). Two of the 12 AK cases had weak-to-moderate positive reactions in the basal, spinous, and horny layers for p16(INK4a). CONCLUSION: The results of our study advance our understanding of the pathogenesis of SCC developing from AK. The results also indicate a differential role in the control of K14 in normal epithelia, AK, and SCC. K14 expression in the spinous and granular layers may be a prognostic factor for tumor progression of AK.

Pathological study of radial sclerosing lesions / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the pathological diagnostic features and the differential diagnosis of radial sclerosing lesions of the breast.</p><p><b>METHODS</b>Morphological observation and immunohistochemistry were applied to forty-four cases of radial sclerosing lesions of the breast.</p><p><b>RESULTS</b>All forty-four patients were females, the mean age was 40.3 years (range 17 to 54 years). In the 31 consultation cases, 13 were misdiagnosed as carcinoma. The lesions had a radiating outline, and a central scar area where squeezed or pressed irregular shaped tubules were frequently seen. Dilated tubules and proliferated ducts or lobules were seen radically arranged at the periphery accompanied sometimes with the apocrine glands or columnar cell metaplasia and hyperplasia. Aside, there were 14 cases displaying necroses and 8 cases showing atypical ductal hyperplasia. Immunostaining showed myoepithelial cells around the pseudo-infiltrating tubules, and the florid proliferating epithelial cells were positive for CK5/6.</p><p><b>CONCLUSIONS</b>Radial sclerosing lesions of the breast possess characteristic histological features, and may be misdiagnosed as carcinoma. The lesions should be differentiated from ductal carcinoma in situ, lobular neoplasia, tubular carcinoma and invasive ductal carcinoma.</p>

A Case of Ectopic Sebaceous Glands in the Esophagus / 대한소화기내시경학회지

A 42-year-old man without any signs or symptoms of illness underwent esophagogastroduodenoscopy (EGD) for a routine health check up. On esophagogastroduodenoscopy, multiple small and yellowish mucosal plaques were detected in the mid to distal esophagus. These plagues proved to be ectopic sebaceous glands of the esophagus according to the histologic examination. On the immunohistochemical staining with anti-Keratin 14, the basal cells and the heterotopic sebaceous glands were immunoreactive for keratin 14. The histogenesis of this extremely rare lesion is not completely clear. There have been some reports on ectopic esophagus sebaceous glands combined with esophageal cancer or gastric cancer. However, malignant transformation of the ectopic sebaceous gland itself has not yet been reported on. This case was regularly followed up for 12 months, and no interval change or malignant transformation was found both endoscopically and histologically.

Expression of fascin and CK14 in different histological types of cancer and its differential diagnostic significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate and analyze the expression of fascin and CK14 in multiple histological types of cancer and to explore the potential value of the two proteins as markers in diagnosis and differential diagnosis of various cancer types.</p><p><b>METHODS</b>Tissue microarray containing esophageal squamous cell carcinoma (SCC), lung SCC, larynx SCC, uterine cervical SCC, SCC of external genital organs, lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, heptocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating ductal carcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma and renal clear cell carcinoma, 30 cases each, as well as corresponding normal controls was constructed. The expression of fascin and CK14 among different types of carcinoma and corresponding normal controls was detected by immunohistochemistry.</p><p><b>RESULTS</b>In normal esophagus, bronchus, larynx, uterine cervix and skin, fascin was mainly expressed in the basal cells or reserve cells, but the expression was diffuse in esophageal SCC, lung SCC, larynx SCC, uterine cervical SCC and SCC of external genital organs, with a positive rate of 90.0%, 90.0%, 96.7%, 78.6% and 89.7%, respectively. In the normal tissue of other organs, except breast and uterine endometrium, fascin was negative. In lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating dutal adenocarcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma and renal clear cell carcinoma, the positive rates were 38.0%, 23.3%, 14.3%, 10.3%, 73.3%, 13.3%, 6.7%, 60.0%, 66.7% and 10.0%, respectively. The difference between fascin expression in SCC and in other histological types was statistically significant (P < 0.001). CK14 was mainly expressed in the basal cells, reserve cells or myoepithelia of normal tissues. The positive rates of CK14 were 76.7%, 36.7%, 83.3%, 60.7% and 96.3% in esophageal SCC, lung SCC, larynx SCC, uterine cervical SCC and SCC of external genital organs, respectively. It was weak and focal in lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating dutal adenocarcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma, and renal clear cell carcinoma, with a positive rate of 13.3%, 13.3%, 20.7%, 41.4%, 46.7%, 6.7%, 40.0%, 13.3%, 20.0% and 6.7%, respectively. The difference between CK14 expression in SCC and in other histological types was statistically significant (P < 0.001). The difference between co-expression of fascin/CK14 in SCC and in other histological types was also statistically significant (P < 0.001).</p><p><b>CONCLUSION</b>Fascin and CK14 are highly expressed in SCC, compared with other histological types of carcinoma. Combination of fascin and CK14 should be a valuable marker in diagnosis and differential diagnosis of carcinoma.</p>

Clinicopathologic study of centrally necrotizing carcinoma of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and immunophenotype of centrally necrotizing carcinoma (CNC) of breast; and to study its relationship with basal-like breast cancer.</p><p><b>METHODS</b>The clinical and pathologic characteristics of 35 cases of CNC were analyzed. Immunohistochemical study for estrogen receptor, progesterone receptor, HER2, CK8/18, 34betaE12, CK5/6, CK14, CK17, smooth muscle actin, p63, vimentin and epidermal growth factor receptor was performed using EnVision method. The surival information of 10 case were obtained.</p><p><b>RESULTS</b>The age of patients with CNC ranged from 30 to 82 years (mean = 54.2 years). Macroscopically, all tumors were relatively circumscribed, with a mean diameter of 2.4 cm. Histologically, there was a prominent central, necrotic or acellular zone surrounded by a narrow rim of viable tumor cells. The central necrotic foci had the following morphologic patterns: (1) coagulative tumor necrosis associated with various degree of fibrosis or hyaline degeneration (24 cases), (2) predominance of fibrous and scar tissue, with small amount of necrotic debris (8 cases), and (3) infarction (3 cases). The peripheral zone of tumor cells showed features of grade 3 invasive ductal carcinoma in 32 cases and grade 2 in 3 cases. Twenty cases of CNC were associated with ductal carcinoma in-situ. A component of invasive micropapillary carcinoma was identified in 5 cases. Peripheral lymphocytic infiltrates were seen in 17 cases. Immunohistochemical study of 31 cases showed that the expression rate of basal-like markers (83.9%, 26 cases) was higher than that of myoepithelial markers (38.7%, 12 cases). The percentage of basal-like subtype (64.5%, 20 cases) was higher than luminal-A (9.7%, 3 cases), luminal-B (9.7%, 3 cases), HER2 over-expression (12.9%, 4 cases) and null (3.2%, 1 case) subtypes. In 20 cases of basal-like carcinoma, the expression ratio of CK5/6 was highest amongst basal-like markers (18 cases), the other markers ratios of CK17, CK14 and epidermal growth factor receptor were 8/10, 14/19 and 8/16, respectively. Follow-up data were available in 10 patients. The follow-up duration ranged from 15 to 42 months (mean = 21.5 months). The median disease-free and overall survivals were 14.0 and 18.0 months, respectively. Disease progression (as defined by the presence of recurrence, metastasis or tumor-related death) occurred in 9 patients. The mean and median time to disease progression was 16.6 and 13.0 months, respectively.</p><p><b>CONCLUSIONS</b>CNC is a rare subtype of breast carcinoma and has distinctive, easily discernible morphologic features. The majority of CNC exhibits basal-like immunophenotype and carries a poor prognosis. CNC is the typical representative of basal-like breast cancer.</p>