Study of Immunohistochemistry in Prostatic Lesions with Special Reference to Proliferation and Invasiveness

Manna, Amalesh Kumar; Pathak, Swapan; Gayen, Prosenjit; Sarkar, Diptendra Kumar; Kundu, Anup Kumar

doi:10.1007/s12262-010-0180-7

Cited by 9 publications

(8 citation statements)

References 14 publications

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“…High-molecular-weight keratins (HMW-CK) include CK1, CK5, CK10 and CK14, which can be recognized by monoclonal antibody 34?12 we used in this study. Among these cytokeratins, CK5 and CK14 are two widely used markers for the basal epithelial phenotype and for the basal-like breast cancer, which is often associated with poor prognosis and invasion phenotype [ 23 ]. Therefore, we investigated the relationships of LKB1 to E-cadherin and HMW-CK in clinical breast cancer tissues, hoping to reveal the role of LKB1 in breast cancer progression.…”

Section: Resultsmentioning

confidence: 99%

Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Liu

et al. 2014

J Exp Clin Cancer Res

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BackgroundLKB1, also known as STK11, is a master kinase that serves as an energy metabolic sensor and is involved in cell polarity regulation. Recent studies have indicated that LKB1 is related to breast tumorigenesis and breast cancer progression. However, little work has been done on the roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer. In this study, we tried to prove that loss of LKB1 disrupts breast epithelial cell polarity and causes tumor metastasis and invasion.MethodsThe relationships of LKB1 expression to clinic-pathological parameters and epithelial markers E-cadherin and high-molecular-weight -cytokeratin (HMW-CK) were investigated in 80 clinical breast cancer tissue samples and their paired normal control breast tissue samples by using immunohistochemistry. Then, the LKB1 expressions in metastatic and non-metastatic breast cancer cell lines were compared. The roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer were determined by using immunofluorescence, western blot assay, and cell migration and invasive assays. Finally, the non-transformed human breast cell line MCF-10A was cultured in three dimensions to further reveal the role of LKB1 in breast epithelial cell polarity maintenance.ResultsHistopathological analysis showed that LKB1 expression level was significantly negatively correlated with breast cancer TNM stage, and positively correlated with ER/PR status and expression levels of E-cadherin and HMW-CK. Immunofluorescence staining showed that LKB1 was co-localized with E-cadherin at adheren junctions. In vitro analysis revealed that loss of LKB1 expression enhanced migration, invasion and the acquisition of mesenchymal phenotype, while LKB1 overexpression in MDA-MB-435 s cells, which have a low basal level of LKB1 expression, promoted the acquisition of epithelial phenotype. Finally, it was found for the first time that endogenous LKB1 knockdown resulted in abnormal cell polarity in acini formed by non-transformed breast epithelial cells grown in 3D culture.ConclusionOur data indicated that low expression of LKB1 was significantly associated with established markers of unfavorable breast cancer prognosis, such as loss of ER/PR, E-cadherin and HMW-CK. Knockdown of endogenous LKB1 gave rise to dysregulation of cell polarity and invasive phenotype of breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Liu

et al. 2014

J Exp Clin Cancer Res

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“…Negative staining must be interpreted with caution because cytokeratin is formalin sensitive and a progressive loss of immunoreactivity can be seen in prolonged formalin fixation. AMACR showed a continuous dark diffuse cytoplasmic staining or circumferential apical granular staining pattern in malignant prostatic lesions but little or no immunoreactivity in benign lesions [ 20 ] ( Figs. 1 – 3 ).…”

Section: Discussionmentioning

confidence: 99%

Histopathological spectrum of 364 prostatic specimens including immunohistochemistry with special reference to grey zone lesions

Garg

Kaur

Malhotra

et al. 2013

Prostate International

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Purpose:Prostatic lesions on routine staining sometimes cause a diagnostic dilemma, especially when malignant tissue is limited and is mixed with benign prostatic glands or because of the presence of benign mimickers of carcinoma. The application of immunohistochemistry contributes a valuable differential diagnosis. This study aimed to evaluate a complete spectrum of various prostatic lesions and to supplement the histopathological diagnosis with immunohistochemistry in suspicious or atypical cases.Methods:A total of 364 consecutive prostatic specimens were evaluated. Routine hematoxylin and eosin staining and immunohistochemical staining against 34βE12 cytokeratin and proliferative marker (alpha-methylacyl-CoA-racemase, AMACR) were performed by use of the peroxidase antiperoxidase method.Results:Benign prostatic hyperplasia was the most frequent finding and involved 285 patients (78.3%). Prostatitis (majority nonspecific) formed the predominant subgroup in nonneoplastic lesions (n=119, 32.7%). The incidence of carcinoma was low (n=73, 20.1%). Of the 26 atypical or suspicious cases, 18 cases were positive for high molecular weight cytokeratin (high molecular weight cytokeratin, HMWCK) only, 4 cases were positive for AMACR only, and 4 cases showed positivity for both HMWCK and AMACR.Conclusions:Biopsy remains the gold standard. However, as an adjunct to biopsy, proliferative markers and basal cell markers have value for resolving suspicious or atypical cases.

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“…High-molecular-weight keratins (HMW-CK) include CK1, CK5, CK10 and CK14, which can be recognized by monoclonal antibody 34β12 we used in this study. Among these cytokeratins, CK5 and CK14 are two widely used markers for the basal epithelial phenotype and for the basal-like breast cancer, which is often associated with poor prognosis and invasion phenotype [23]. Therefore, we investigated the relationships of LKB1 to E-cadherin and HMW-CK in clinical breast cancer tissues, hoping to reveal the role of LKB1 in breast cancer progression.…”

Section: Resultsmentioning

confidence: 99%

Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Liu

Yang

et al. 2014

J Exp Clin Cancer Res

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Background: LKB1, also known as STK11, is a master kinase that serves as an energy metabolic sensor and is involved in cell polarity regulation. Recent studies have indicated that LKB1 is related to breast tumorigenesis and breast cancer progression. However, little work has been done on the roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer. In this study, we tried to prove that loss of LKB1 disrupts breast epithelial cell polarity and causes tumor metastasis and invasion. Methods: The relationships of LKB1 expression to clinic-pathological parameters and epithelial markers E-cadherin and high-molecular-weight -cytokeratin (HMW-CK) were investigated in 80 clinical breast cancer tissue samples and their paired normal control breast tissue samples by using immunohistochemistry. Then, the LKB1 expressions in metastatic and non-metastatic breast cancer cell lines were compared. The roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer were determined by using immunofluorescence, western blot assay, and cell migration and invasive assays. Finally, the non-transformed human breast cell line MCF-10A was cultured in three dimensions to further reveal the role of LKB1 in breast epithelial cell polarity maintenance.

show abstract

Study of Immunohistochemistry in Prostatic Lesions with Special Reference to Proliferation and Invasiveness

Cited by 9 publications

References 14 publications

Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Histopathological spectrum of 364 prostatic specimens including immunohistochemistry with special reference to grey zone lesions

Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

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