1.p16INK4a protein is a specific molecular biomarker of breast cancer.
Jun YANG ; Xiao-Zhong HUANG ; Rui GUO ; Ying HUANG ; An-Jing KANG ; Yao-Feng JIN ; Xiao-Li CHEN ; Zong-Fang LI
Journal of Southern Medical University 2016;36(6):751-755
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
2.Value of CK5/6, CK14, ER and PR detection in differential diagnosis of intraductal proliferative lesions of the breast.
Fengting NIU ; Li WANG ; Wei ZHANG ; Shuhua LYU ; Yun NIU ; Email: YUNNIU2000@126.COM.
Chinese Journal of Oncology 2015;37(10):749-752
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
3.Expression of p63, p40 and CK5/6 in small cell lung cancer.
Liping ZHANG ; Likun HOU ; Huikang XIE ; Zhengwei DONG ; Wei WU ; Jie KONG ; Gang CHEN ; Chunyan WU ; E-mail: WUCHUNYAN581@SINA.COM.
Chinese Journal of Pathology 2015;44(9):644-647
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
4.Clinicopathologic features of cystic hypersecretory lesion of the breast.
Rui BI ; Yufan CHENG ; Baohua YU ; Ruohong SHUI ; Wentao YANG ; Xiaoli XU ;
Chinese Journal of Pathology 2014;43(1):25-29
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
5.Clinicopathologic features and immunohistochemistry of the basal-like subtype of invasive breast carcinoma.
Li-ping LIU ; Jun BAI ; Ya WEI ; Xiao-dong QI ; Ting-chen SI ; Wei LI ; Hui PAN
Chinese Journal of Pathology 2013;42(2):101-105
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
6.The breast stem cell (CK5/6(+)) concept and its relation to the diagnosis of benign and malignant ductal epithelial hyperplasia.
Chinese Journal of Pathology 2013;42(2):73-77
Breast
;
pathology
;
Carcinoma, Intraductal, Noninfiltrating
;
diagnosis
;
metabolism
;
pathology
;
Female
;
Humans
;
Hyperplasia
;
metabolism
;
pathology
;
Keratin-5
;
metabolism
;
Keratin-6
;
metabolism
;
Precancerous Conditions
;
diagnosis
;
metabolism
;
pathology
;
Stem Cells
;
metabolism
;
pathology
7.Invasive lobular carcinoma of basal-like subtype of breast: a clinicopathologic analysis.
Li-ying ZHANG ; Lan-xiang GAO ; Guang LIU ; Guang-zhi YANG ; Juan CHENG ; Hua-ye DING
Chinese Journal of Pathology 2013;42(9):599-603
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
8.Keratocytoma of submandibular gland:report of a case.
Ji-man LI ; Ying WANG ; Jin-chuan FAN ; Mei TANG ; Jun HOU ; Lun LI
Chinese Journal of Pathology 2013;42(12):838-839
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
9.Papillary lesions of the breast.
Chinese Journal of Pathology 2013;42(11):721-726
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
10.Pathologic diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of breast and syringomatous adenoma of nipple.
Jing LI ; Guang-zhi YANG ; Hua JIN ; Hua-ye DING
Chinese Journal of Pathology 2012;41(5):301-304
OBJECTIVETo investigate the pathologic and immunohistochemical features, diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple.
METHODSSix 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.
RESULTSThe 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.
CONCLUSIONSLow-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.
Adenocarcinoma ; pathology ; Adult ; Aged ; Breast ; pathology ; Breast Neoplasms ; diagnosis ; metabolism ; pathology ; Carcinoma, Adenosquamous ; diagnosis ; metabolism ; pathology ; Carcinoma, Squamous Cell ; pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Middle Aged ; Neprilysin ; metabolism ; Nipples ; pathology ; Sclerosis ; Sweat Gland Neoplasms ; diagnosis ; metabolism ; pathology ; Syringoma ; diagnosis ; metabolism ; pathology ; Transcription Factors ; metabolism ; Tumor Suppressor Proteins ; metabolism

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