The Amelioration Effect of the Ethanolic Extract of Cnidium officinale in Mice with Imiquimod-induced Psoriasis-like Skin Lesion

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.

p16INK4a protein is a specific molecular biomarker of breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of p16INK4a protein in breast cancer and analyze its clinical significance.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>The 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.</p>

A novel H1 mutation in keratin 6a in an infant with pachyonychia congenita.

Pachyonychia congenita (PC) is a rare genetic disorder which is inherited in an autosomal dominant pattern. We report a sporadic novel H1 mutation in the KRT6A gene (c. 428G>A/p. Ser143Asn) in a Chinese infant patient. The mutation is concurrent with a single-nucleotide polymorphism and resulted in a serine for asparagine substitution in H1 subdomain of KRT6A chain next to the rod domain. The infant showed the classic symptoms of pachyonychia congenita. Conclusion: The heterozygous missense mutation c. 428G > A/p.Ser143Asn in KRT6A exon 1 may cause severe disease

Expression of p63, p40 and CK5/6 in small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC).</p><p><b>METHODS</b>Immunohistochemical 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSIONS</b>p63 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.</p>

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>

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>

Invasive lobular carcinoma of basal-like subtype of breast: a clinicopathologic analysis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features, clinical progress and prognosis of the basal-like subtype of invasive lobular carcinoma (ILC) of the breast.</p><p><b>METHODS</b>Four 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.</p><p><b>RESULTS</b>Morphologically, 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.</p><p><b>CONCLUSIONS</b>ILC 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.</p>

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>

Pathologic diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of breast and syringomatous adenoma of nipple / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the pathologic and immunohistochemical features, diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple.</p><p><b>METHODS</b>Six cases of low-grade adenosquamous carcinoma of the breast and four cases of syringomatous adenoma of the nipple were examined histologically and immunohistochemically (MaxVision method), and the literature was reviewed.</p><p><b>RESULTS</b>The two types of tumors were similar in morphology, but located in different regions with low-grade adenosquamous carcinoma being present in the deep parenchyma and syringomatous adenoma in nipple. Both types of tumors were composed mainly of well-differentiated glands with angulated, comma shaped or polliwog appearance in a disordered infiltrative pattern. The tumor cells also formed solid tubules, strips or nests, with frequent areas of squamoid differentiation. Mitosis was rare. The interstitial tissue showed abundant spindle cells or sclerotic fibrosis with mixed inflammatory cells infiltration. One case of low-grade adenosquamous carcinoma showed a concomitant malignant adenomyoepithelioma, and another case showed concomitant spindle cell metaplastic carcinoma. One case of syringomatous adenoma involved the deep parenchyma. Immunohistochemistry of low-grade adenosquamous carcinoma showed that CK5/6 and p63 were positive in the outer layer of the glands and the squamoid epithelium, and CD10 was also positive in the outer layer of the glands. ER and HER2 were negative, and PR was also negative except for one case in which the spindle cells were positive for CK5/6, AE1/AE3 and PR focally. Immunostaining of syringomatous adenoma demonstrated that p63 and CK5/6 were positive in the outer layer of the glands and the squamoid epithelium. Calponin, SMA, ER, PR and HER2 were all negative.</p><p><b>CONCLUSIONS</b>Low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple are similar in morphology and immunohistochemical phenotype, while the biological features are opposite due to different locations. The differential diagnoses include tubular carcinoma, adenosquamous carcinoma, radial sclerosing lesions and others.</p>

Clinicopathlogic and Immunohistochemical Characteristics of Triple Negative Invasive Lobular Carcinoma

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.

Clinicopathologic features of endolymphatic sac tumor at cerebellopontine angle / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and immunophenotype of endolymphatic sac tumor (ELST) and normal endolymphatic sac.</p><p><b>METHODS</b>The clinical and histologic features were evaluated in 5 cases of ELST. Eight cases of choroid plexus papilloma at cerebellopontine angle and 2 cases of normal endolymphatic sac were used as controls. Immunohistochemical study for vimentin, AE1/AE3, CK8/18, CK5/6, EMA, GFAP, synaptophysin, S-100 protein, CEA, TTF-1, VEGF, D2-40, calponin, calretinin and Ki-67 was carried out.</p><p><b>RESULTS</b>The age of onset of ELST ranged from 23 to 35 years (median = 24 years). The male-to-female ratio was 2:3. The clinical presentation was tinnitus, otalgia, hearing loss, otorrhagia with effusion and headache. The duration of symptoms ranged from 6 months to 10 years. Local recurrences were noted in 3 cases. Radiologically, the tumors were located at cerebellopontine angle and demonstrated petrous bone destruction. Histologic examination showed that the tumors had a papillary-glandular pattern. The papillae were covered by a single layer of low cuboidal cells. The tumor cells had distinct cell borders and contained eosinophilic to clear cytoplasm. The nuclei were slightly atypical and sometimes apically located. Focal dilated glandular structures with colloid-like material were also identified. The surrounding stroma was vascularized. All of the 5 cases had dural or petrous bone infiltration. Immunohistochemical study showed that all of the 5 cases were positive for AE1/AE3, CK8/18, CK5/6 and VEGF, 4 cases for EMA, 3 cases for calponin (focal), 2 cases for vimentin, 2 cases for S-100 protein, 1 case for GFAP and 1 case for synaptophysin (focal and weak). The Ki-67 index measured less than 1%. The staining for D2-40, calretinin, CEA and TTF-1 was negative. The 2 cases of the normal endolymphatic sac were positive for AE1/AE3 and CK8/18, and negative for CK5/6, EMA, S-100 protein, GFAP and synaptophysin. The 8 cases of choroid plexus papilloma were positive for synaptophysin. Seven cases were also positive for S-100 protein, 2 cases for GFAP and 1 case for D2-40. All of the 8 cases were negative for EMA, CK5/6 and calponin.</p><p><b>CONCLUSIONS</b>ELST is a rare slow-growing and potentially malignant tumor with a tendency of bone invasion and local recurrence. Distant metastasis is not observed. It must be distinguished from choroid plexus papilloma occurring at cerebellopontine angle. Correlation with clinical, radiologic and immunohistochemical findings would also be helpful.</p>

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>

Relationship between breast cancer molecular subtypes with clinicopathological characteristics and prognosis / 中华病理学杂志

<p><b>OBJECTIVES</b>This study try to subclassify breast cancer into different prognostic subgroups according to immunohistochemical algorithm and discuss the relationship between subtypes and biological and clinical behavior and prognosis.</p><p><b>METHODS</b>One hundred and twenty-eight cases of infiltrative ductal carcinoma were studied using immunohistochemical staining with an antibody panel of ER, PR, HER2 and CK5/6 and subclassified referring to previous reports, and the 9 cases of HER2 positive subtype were tested using FISH.</p><p><b>RESULTS</b>The expression of ER, PR, HER2, and CK5/6 was detected in 67%, 45%, 27% and 27% cases, respectively. All cases were subclassified into five subgroups, with luminal A (55%), luminal B (20%), HER2 positive (7%), basal-like (10%) and unclassified cases (8%). Nine HER2 positive cases all showed amplification of HER2 gene. It was demonstrated that the luminal A group was associated with the best prognosis but the basal-like group worst by univariate analysis. Multivariate analysis demonstrated that both the clinical stage and immunohistochemical subtypes of tumor were related to overall survival. Menses status were different among these subtypes.</p><p><b>CONCLUSION</b>According to the expression of ER, PR, HER2 and CK5/6, infiltrative ductal carcinoma could be subclassified into five subgroups with different biological features and outcome, having a role in evaluating the prognosis and guiding the clinical treatment.</p>

The 521 T--> C mutation in the keratin 6A gene in a pedigree with pachyonychia congenita type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the mutation in the keratin 6A(K6A) gene in a pedigree with pachyonychia congenita type I (PC-I).</p><p><b>METHODS</b>Blood samples were obtained from 2 affected, 3 unaffected members in this family, and 100 unrelated healthy individuals. Mutation detection was carried out by PCR amplification of the K6A gene and direct DNA sequencing.</p><p><b>RESULTS</b>A heterozygous mutation of T--> C transition at position 521 in exon 1 of the K6A gene was found in the 2 affected, but not in the unaffected members and 100 unrelated healthy individuals.</p><p><b>CONCLUSION</b>The mutation of 521T--> C in the K6A gene is the disease causing mutation in this PC-I family.</p>

Expression of basal and luminal cytokeratins in breast cancer and their correlation with clinicopathological prognostic variables.

Background : Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns. The aim of this study is to evaluate the expression of some prognostic biomarkers (ER, PR and HER2), as well as histological grading and lymph node status in cytokeratin-based groups of breast cancer. Objective: To evaluate the correlation between expression of basal and luminal markers and hormonal receptors, HER2/neu, age, grade and lymph node status in breast-invasive ductal carcinoma. Materials and Methods : Sixty-seven formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma, 'NOS' type) which had already been studied for ER, PR and HER2/neu were selected. Data concerning age, tumor grade and lymph node status were also obtained from archives. Expression of basal (CK5/6) and luminal (CK7) cytokeratins was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of stained cells. Results : We categorized the cases into 3 distinct phenotype groups: pure luminal, basal phenotype and null. Pure basal, mixed basal and luminal groups were classified as expressing a basal phenotype. There was a significant difference in the ER and/or PR expression between those 3 groups and a significant association between ER and/or PR negativity and basal phenotype expression. There was no significant difference in HER2/neu expression, age of the patients, tumor grade and lymph node status between the 3 cytokeratin-based groups and no significant association between lymph node status and basal phenotype expression. Conclusion : We found that to gain a real association between basal phenotype and prognostic markers, we should use a cocktail or a panel of different biomarkers to correctly determine basal-like phenotype of breast cancers. This approach guarantees more concordance with gene expression-based studies.

Roles of immunohistochemistry in prognostic assessment of basal-like breast cancer / 中华病理学杂志

<p><b>OBJECTIVES</b>Basal cell-like breast cancer is one of the subtypes using molecular typing, and this subtype attracted a wide spread attention. Currently, no uniform diagnostic criteria are available. Most studies demonstrated poor outcomes, but contradictory conclusions appeared recently. The prognosis of basal cell-like breast cancer using different immunohistochemical criteria were analyzed.</p><p><b>METHODS</b>Two hundred and eighty-four invasive breast cancers with a follow-up information over 5 years were evaluated for ER, PR, HER2, CK5/6, CK14, EGFR expression on tissue microarray immunohistochemically. Based on the results, these cases using four different diagnostic criteria were categorized, namely: Nielsen (ER-/HER2-, CK5/6+ and/or EGFR+), Kim (ER-/PR-/HER2-, CK5/6+ and/or CK14+ and/or EGFR+), Triple-negative (ER-/PR-/HER2-), and basal-CK (CK5/6+ and/or CK14+). 5-year survival information was compared between groups.</p><p><b>RESULTS</b>The prevalence of basal cell-like breast cancer by Nielsen, Kim, Triple-negative and basal-CK were 15.5% (44/284), 14.8% (42/284), 43.3% (123/284) and 21.1% (60/284) respectively; the recurrence rates were 18.2% (8/44), 21.4% (9/42), 10.6% (13/123) and 11.7% (7/60) respectively. These were higher than recurrence rates for other subtypes, but only the differences by Nielsen's and Kim's criteria were significant. Using Nielsen's and Triple-negative's criteria, basal-like tumors showed shorter 5-year disease-free survival (both P < 0. 01) and overall survival (P < 0.05 and 0.01) than luminal A subtype, using Kim's criteria, basal-like tumors showed a lower 5-year disease-free but not overall survival than luminal A subtype (P < 0.01); no significant difference was found on 5-year survival between basal-like and non-basal-like tumors when typed by basal-CK.</p><p><b>CONCLUSION</b>Basal cell-like breast cancers are more likely to show more recurrence and worse outcome, but different immunohistochemical diagnostic criteria have an influence on their prognostic analysis, so a uniform diagnostic criteria is essential for the further study of basal-like breast cancers.</p>

Two mutations of the KRT6A gene in Chinese patients with pachyonychia congenita type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type I(PC-1), as well as to explore the relationship between the genotype and phenotype.</p><p><b>METHODS</b>The whole coding region of the KRT16 and KRT6A genes were amplified by long-range polymerase chain reaction (PCR). Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorphism. PCR products were directly sequenced to detect the mutation.</p><p><b>RESULTS</b>No mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at codon 465 (TAC to CAC) which substitutes tyrosine (Y) by histidine (H). In the sporadic patient, codon 171 (AAC) was mutated to GAC, which changes the asparagines (N) to aspartic acid (D). No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations.</p><p><b>CONCLUSION</b>The mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.</p>

Analysis of human hair basic keratin 6 gene mutation in a Chinese Han family with monilethrix / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the human hair basic kerat in 6 gene (hHB6) gene mutation in a mother and her daughter with monilethrix.</p><p><b>METHODS</b>Clinical data were obtained by investigating the pedigree and examining the patients' hair and skin. Total genomic DNA of the family participants was isolated. All exons and exon-intron boundaries of hHB6 were amplified by PCR. Mutation screening was carried out using direct DNA sequencing. Restriction fragment length polymorphism (RFLP) analysis was used to confirm the mutation, and to investigate if the mutation co-segregated with the disease in the family and existed in normal controls.</p><p><b>RESULTS</b>A heterozygous transition of c.1204G to A (p.E402K) of hHB6 was identified. RFLP analysis demonstrated that affected members carried the p.E402K mutation, but the unaffected members of the family and 150 unrelated normal Chinese Han nationality controls did not carry the mutation.</p><p><b>CONCLUSION</b>This study identified the hHB6 gene mutation c.1204G to A (p.E402K) in a Chinese monilethrix family. The mutation was inherited from the mother to her daughter. The results emphasized the key role of hair keratin hHB6 in the pathogenesis of monilethrix and indicated that the common mutation of hHB6 was also a cause of monilethrix in Chinese.</p>

Expression of CK5/6 and CK17 and its correlation with prognosis of triple-negative breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation of CK5/6 and CK17 expression with clinical outcome in patients with triple-negative [ER(-), PR(-), Her-2(-)] breast cancer.</p><p><b>METHODS</b>112 patients with breast cancer treated by surgery between 2000 and 2002 were included in this study. All cases were immunohistochemically proven to be triple-negative. Samples of formalin-fixed and paraffin-embedded surgical specimens were obtained for immunohistological examination for CK5/6 and CK17 expression. The correlation of the gene expression with clinicopathological features and outcome of the patients was analyzed.</p><p><b>RESULTS</b>Of the 112 triple-negative patients, five-year disease-free survival rate was 73.2% (82/112). The positive rate of both CK5/6 and CK17 was 21.4% (24/112), either CK5/6 or CK17 positive was 46.4% (52/112). It was shown by Kaplan-Meier curve that positive CK5/6, CK17 or CKs (CK5/6 or CK17 positive) was correlated with poor five-year disease-free survival (P = 0.020, P = 0.032, P = 0.003); and positive staining of CK5/6 or CKs was correlated with poor five-year overall survival (P = 0.027, P = 0.015). Of the 91 patients with invasive ductal carcinoma, a correlation of CK5/6 or CK17 positive staining with high grade differentiation was observed (P = 0.030), and with axillary lymph node metastasis was also noticed (P = 0.044). Multivariate analysis by Cox regression showed that differentiation grade, pathological stage and expression of CK5/6 were factors affecting both the disease-free-survival and overall-survival, while menopausal status was an independent factor affecting the disease-free-survival.</p><p><b>CONCLUSION</b>Positive expression of CK5/6 or CK17 in patients with triple-negative breast cancer is correlated with poor prognosis, high grade differentiation and axillary lymph node metastasis.</p>

Expression of the Markers for the Mammary Stem Cells and the Cellular Lineages of the Mammary Gland on Ductal Carcinoma In Situ / 한국유방암학회지

PURPOSE: Breast Cancer is an inter-tumoral and intra-tumoral heterogeneous disease. It remains unclear whether this heterogeneity results from different target cells or from different subsets of genetic abnormalities, otherwise from both. We postulated that in addition to genetic cloning, a variety of cells that exist during the defined developmental stages of the human mammary gland could give rise to the heterogeneity of breast cancer. To verify this postulation, we have analyzed pure ductal carcinoma in situ (DCIS) for the expression of the biomarkers that represent the mammary stem cell, the early progenitor cells, and the glandular and myoepithelial cells of the mammary gland. METHODS: We investigated the relationship between the immnuohistochemical expression of the mammary development-associated biomarkers {cytokeratin-18 (CK18), cytokeratin-6 (CK6), alpha-smooth muscle actin (SMA), Wnt-1, Notch 3} and some other factors {the menopausal status, the estrogen receptor (ER) status, the progesterone receptor (PR) status, c-erbB-2, and the number of tumor foci} in 26 cases of DCIS. RESULTS: All 26 cases included in this study showed the positive expressions of CK18 and SMA. The expression of all the markers was not correlated with the menopausal status. The positive expression of CK6 had a statistically significant relationship with a negative estrogen receptor (p=0.014), positive c-erbB-2 (p=0.048), high nuclear grade (p=0.001), and single focus of DCIS (p=0.017). The expression of Wnt-1 and Notch 3 did not have significant correlation with any factors. However, the positive expression of Wnt-1 showed a tendency of a negative ER (p=0.061) and the positive expression of Notch 3 also showed a tendency of a negative ER (p=0.086) and a high nuclear grade (p=0.086). CONCLUSION: The CK6 positive tumor is thought to originate from the more primitive cells compared to the CK6 negative tumor. Unifocality of the CK positive tumor might result from the arrest of differentiation of the original cell after disease affection. DCISs could be categorized into the CK6 positive and negative groups.