Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14⁺ (K14⁺) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14⁺ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140⁺/ K14⁺ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14⁺ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14⁺ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140⁺/K14⁺, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Animals ; Carrier Proteins/metabolism* ; Cell Differentiation ; Keratin-14/metabolism* ; Mice ; Osteogenesis ; Salivary Glands/metabolism* ; Stem Cells

Adenoma, Sweat Gland ; metabolism ; Diagnosis, Differential ; Humans ; Keratin-14 ; metabolism ; Keratin-17 ; metabolism ; Keratin-18 ; metabolism ; Keratin-7 ; metabolism ; Keratins ; metabolism ; Papilloma ; metabolism ; Sebaceous Gland Neoplasms ; metabolism ; Skin Neoplasms ; metabolism ; Sweat Gland Neoplasms ; 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

Acanthoma ; metabolism ; pathology ; surgery ; Adenoma ; metabolism ; pathology ; Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Keratosis ; metabolism ; pathology ; surgery ; Male ; Poroma ; classification ; metabolism ; pathology ; surgery ; Sweat Gland Neoplasms ; classification ; metabolism ; pathology ; surgery

OBJECTIVETo evaluate the diagnostic approach and criteria for intraductal papillary neoplasms of breast.

METHODSAccording 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.

RESULTSAmongst 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.

CONCLUSIONSIntraductal 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.

Adult ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Keratin-7 ; metabolism ; Mammaglobin A ; metabolism ; Middle Aged ; Neprilysin ; metabolism ; Papilloma, Intraductal ; metabolism ; pathology ; Transcription Factors ; metabolism ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo investigate the clinicopathologic features and immunohistochemical of the basal-like subtype of invasive breast carcinoma (BLBC), and to discuss the diagnosis standard.

METHODSImmunohistochemistry 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.

RESULTSAmong 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).

CONCLUSIONBLBC showed distinct morphologic and immunophenotypic features.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; Breast Neoplasms, Male ; metabolism ; pathology ; Carcinoma, Basal Cell ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-17 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo investigate the different location and the expression characteristics of epidermal stem cells in normal adult skin and scar tissue.

METHODSSkin tissue specimens were harvested from the corresponding sites from 6 healthy volunteers and from scar tissue of 6 patients 1 year after major deep burn. beta1 integrin and keratin 19 (K19) were employed as the biochemical markers for stem cells and transit amplifying cells identification and keratin 14 (K14) and keratin 10 (K10) as markers for post-mitotic cells and terminally differentiated cells respectively. Integrin and keratin were determined by Elivision two-step immunohistochemistry.

RESULTSThe expression of beta1 integrin and the K19 positive cell count in the epithelial basal layers of scar tissue were evidently decreased and weakened than those in normal adult healthy skin. Furthermore, the positive cells expressing K14 in epidermis of scar tissue were only located in 2 - 3 layers of basal epidermis, and their number was much less than that in normal adult skin. Whereas the cells positively expressing K10 were distributed wider in area than that in normal healthy skin. The epidermal stem cells and transit amplifying cells in scar epidermis were much less in number than that in normal skin. The differentiation process of scar epidermal stem cells was different from that of normal skin. And the proportions of post-mitotic cells and terminally differentiated cells were abnormal.

CONCLUSIONThe results indicated that the self-renewal ability of the scar epidermis was decreased, and the differentiation process of it was in disorder, which may be a reason for the abnormality of structure and function of the epidermis in scar, and a reason for the decreased ability of wound healing of scar tissue.

Adult ; Burns ; complications ; metabolism ; pathology ; Cicatrix ; etiology ; metabolism ; pathology ; Epidermis ; chemistry ; cytology ; Humans ; Immunohistochemistry ; Integrin beta1 ; analysis ; Keratin-10 ; Keratin-14 ; Keratins ; analysis ; Middle Aged ; Skin ; chemistry ; cytology ; Stem Cells ; chemistry ; cytology

OBJECTIVETo investigate the clinicopathologic and immunohistochemical features as well as the differential diagnoses of the solid variant of mammary adenoid cystic carcinoma with basaloid features.

METHODSClinical 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.

RESULTSThe 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.

CONCLUSIONSThe 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.

Aged ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Adenoid Cystic ; metabolism ; pathology ; surgery ; Carcinoma, Basal Cell ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Small Cell ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-7 ; metabolism ; Mastectomy ; methods ; Middle Aged ; Proto-Oncogene Proteins c-kit ; metabolism ; Vimentin ; 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

OBJECTIVETo investigate the rules of proliferation of epithelial cells of sweat glands in deep partial-thickness burn wound and its transdifferentiation towards epidermal cells during healing process to explore its mechanisms.

METHODSTwenty-eight patients with limbs and trunk burn hospitalized in the Fourth People's Hospital of Taizhou City of Jiangsu Province and the Second Hospital of Shandong University from January 2004 to December 2007 were enrolled in the study. Tissue samples of deep partial-thickness burn wound (DPBW, n = 37), superficial partial-thickness burn wound (SPBW, n = 21), and normal skin (NS, n = 10) were harvested. Expressions of cytokeratin 10 (CK10), bcl-2, P63, CK14 and CK19 of epithelial cells in glandular secretory portion (GSP) in DPBW, SPBW and NS were detected with immunohistochemical double staining method.

RESULTSIn NS, CK19, CK14 and CK10 expressed in medium intensity in GSP epithelial cells, P63 and CK14 weakly expressed in basal myoepithelial cells, while no expression of bcl-2 or P63 was observed in all CK10 positive terminally differentiated cells. In SPBW, no change of the construction of GSP and above-mentioned proteins during healing process was observed. In DPBW, as examined on 7(th) post burn day (PBD), expression of P63 and bcl-2 in GSP epithelial cells was enhanced. In DPBW on 8 - 10 PBD, bcl-2, P63, CK19 and CK14 strongly positive solid island-like epithelial structure was formed by proliferation, migration and squamous epithelization of basal cells. Such structure, along with granulation tissue, migrated towards the superficial layer of wounds. The hyperplasia of squamous epithelium resulted in complete reepithelialization. In DPBW, bcl-2, CK14, CK19 and P63 still strongly expressed in hyper-proliferative epidermal basal and suprabasal layers on 13 - 30 day after healing.

CONCLUSIONSDuring the natural healing process of DPBW, monolayer epithelium (CK19 and CK10 positive) of GSP slowly develops into stratified squamous epithelium (bcl-2, P63, CK19, and CK14 positive), suggesting that the epithelial-epidermal transdifferentiation of GSP undergoes slow retrodifferentiation process of stem cells and transient amplifying cells, resulting in the imbalance between lagged growth of epithelium and the hyperplasia of granulation tissue, constituting one of the important mechanisms of disturbance in DPBW repair.

Adolescent ; Adult ; Burns ; metabolism ; pathology ; Cell Differentiation ; Epithelial Cells ; metabolism ; Female ; Humans ; Keratin-10 ; metabolism ; Keratin-14 ; metabolism ; Keratin-19 ; metabolism ; Male ; Membrane Proteins ; metabolism ; Stem Cells ; metabolism ; Sweat Glands ; cytology ; metabolism ; Wound Healing ; Young Adult ; bcl-2-Associated X Protein ; metabolism