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1.
Case Rep Urol ; 2023: 7301284, 2023.
Article in English | MEDLINE | ID: mdl-36818742

ABSTRACT

Prostate cancer patients routinely undergo surveillance for recurrence using prostate-specific antigen (PSA). While PSA's benefit in screening is controversial, its use for detecting recurrence in patients with history of prostate cancer is pivotal. Rising PSAs with the newly advanced prostate-specific membrane antigen positron emission tomography (PSMA PET) can help localize the location of recurrences for better excision and management. Here, we present a 55-year-old with prostate cancer, with initially undetectable postprostatectomy PSA levels, who later presented with a PSA of 3.47 ng/mL. PSMA PET showed isolated uptake in an abdominal wall mass. Pelvic lymphadenectomy and abdominal wall mass excision were performed, confirming a single metastasis in an abdominal wall lymph node. Metastasectomy led to a dramatic drop in PSA to 0.10 ng/mL both postoperatively and on long-term follow-up. Our case illustrates the potential benefit of metastasis-directed therapy in delayed oligometastasis following definitive management of prostate cancer.

2.
Oncogene ; 40(37): 5651-5664, 2021 09.
Article in English | MEDLINE | ID: mdl-34326467

ABSTRACT

Metastatic breast cancer causes most breast cancer-associated deaths, especially in triple negative breast cancers (TNBC). The metastatic drivers of TNBCs are still poorly understood, and effective treatment non-existent. Here we reveal that the presence of Aurora-A Kinase (AURKA) in the nucleus and metastatic dissemination are molecularly connected through HIF1 (Hypoxia-Inducible Factor-1) signaling. Nuclear AURKA activates transcription of "hypoxia-induced genes" under normoxic conditions (pseudohypoxia) and without upregulation of oxygen-sensitive HIF1A subunit. We uncover that AURKA preferentially binds to HIF1B and co-localizes with the HIF complex on DNA. The mass-spectrometry analysis of the AURKA complex further confirmed the presence of CBP and p300 along with other TFIIB/RNApol II components. Importantly, the expression of multiple HIF-dependent genes induced by nuclear AURKA (N-AURKA), including migration/invasion, survival/death, and stemness, promote early cancer dissemination. These results indicate that nuclear, but not cytoplasmic, AURKA is a novel driver of early metastasis. Analysis of clinical tumor specimens revealed a correlation between N-AURKA presence and decreased patient survival. Our results establish a mechanistic link between two critical pathways in cancer metastasis, identifying nuclear AURKA as a crucial upstream regulator of the HIF1 transcription complex and a target for anti-metastatic therapy.


Subject(s)
Aurora Kinase A , Cell Communication , Cell Nucleus , E1A-Associated p300 Protein , Humans , Hypoxia-Inducible Factor 1, alpha Subunit , Signal Transduction , Triple Negative Breast Neoplasms
3.
Mol Cancer Res ; 19(5): 784-798, 2021 05.
Article in English | MEDLINE | ID: mdl-33500360

ABSTRACT

Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205. We identified TCF4 as a potential new target of miR200s. Expression of ZEB1/2 strongly correlated with the mesenchymal phenotype in breast cancer cells, with the CD24-/CD44+ stemness profile, and with lower expression of core epithelial genes in human breast tumors. Knockdown of EMT-TFs identified the key role of ZEB1 and its functional cooperation with other EMT-TFs in the maintenance of the mesenchymal state. Inducible ZEB1+2 knockdown in xenograft models inhibited pulmonary metastasis, emphasizing their critical role in dissemination from primary site and in extravasation. However, ZEB1+2 depletion one-week after intravenous injection did not inhibit lung colonization, suggesting that ZEB1/2 and EMT are not essential for macrometastatic outgrowth. These results provide strong evidence that EMT is orchestrated by coordinated expression of several EMT-TFs and establish ZEB1 as a key master regulator of EMT and metastasis in breast cancer. IMPLICATIONS: The EMT program is orchestrated by coordinated expression of multiple EMT transcription factors, whereas ZEB1 integrates the EMT master regulatory network and plays the major role in promoting EMT and metastasis.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Transcription Factors/metabolism , Animals , Breast Neoplasms/genetics , Cell Culture Techniques , Cell Line, Tumor , Cell Proliferation/physiology , Epithelial-Mesenchymal Transition , Female , Heterografts , Humans , Male , Mice , Mice, Inbred NOD , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasm Metastasis , Transcription Factors/genetics , Zinc Finger E-box Binding Homeobox 2/genetics , Zinc Finger E-box Binding Homeobox 2/metabolism , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism
4.
Sci Rep ; 10(1): 6035, 2020 04 07.
Article in English | MEDLINE | ID: mdl-32265483

ABSTRACT

The autosomal dominant presentation of trichilemmal cysts is one of the most common single gene familial diseases in humans. However, the genetic basis for the inheritance and genesis of these lesions has remained unknown. We first studied patients with multiple trichilemmal cysts using exome and Sanger sequencing. Remarkably, 21 of 21 trichilemmal cysts from 16 subjects all harbored a somatic p.S745L (c.2234 G > A) mutation in phospholipase C delta 1 (PLCD1), a proposed tumor suppressor gene. In addition to this specific somatic mutation in their tumors, 16 of the 17 subjects with multiple trichilemmal cysts were also heterozygous for a p.S460L (c.1379 G > A) germline variant in PLCD1 which is normally present in only about 6% of this population. The one patient of 17 that did not show the p.S460L germline variant had a germline p.E455K (c.1363 C > T) mutation in the same exon of PLCD1. Among 15 additional subjects, with a history suggesting a single sporadic trichilemmal cyst, six were likely familial due to the presence of the p.S460L germline variant. Of the remaining truly sporadic trichilemmal cysts that could be sequenced, only half showed the p.S745L somatic mutation in contrast to 100% of the familial cysts. Surprisingly, in contrast to Knudsen's two hit hypothesis, the p.S745L somatic mutation was always on the same chromosome as the p.S460L germline variant. Our results indicate that familial trichilemmal cysts is an autosomal dominant tumor syndrome resulting from two hits to the same allele of PLCD1 tumor suppressor gene. The c.1379 G > A base change and neighboring bases are consistent with a mutation caused by ultraviolet radiation. Our findings also indicate that approximately one-third of apparently sporadic trichilemmal cysts are actually familial with incomplete penetrance. Sequencing data suggests that the remaining, apparently sporadic, trichilemmal cysts are genetically distinct from familial cysts due to a lack of the germline mutations that underlie familial cysts and a decreased prevalence of the p.S745L somatic mutation relative to familial trichilemmal cysts.


Subject(s)
Epidermal Cyst/genetics , Phospholipase C delta/genetics , Cross-Sectional Studies , Genetic Predisposition to Disease , Germ-Line Mutation , Heterozygote , Humans , Point Mutation
5.
Case Rep Oncol ; 12(3): 765-776, 2019.
Article in English | MEDLINE | ID: mdl-31762748

ABSTRACT

Patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) have several EGFR targeting tyrosine kinase inhibitors (TKIs) available in frontline management. However, the disease will inevitably progress over time due to acquired resistance. Longitudinal tumor profiling for genomics guided therapy is indicated upon disease progression. It is a common scenario yet, when after failure of EGFR-TKIs, potentially actionable genomic alterations are lacking. Management of such patient is challenging with very limited options available. Combination of chemotherapy, anti-vascular/anti-angiogenic and immune-checkpoint inhibitors may become a salvage option for such patients. Here we describe a case of TKI refractory EGFR-mutant NSCLC successfully treated with carboplatin, paclitaxel, atezolizumab and bevacizumab combination with remarkable prompt tumor response.

6.
Transl Lung Cancer Res ; 8(5): 700-705, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31737506

ABSTRACT

Epithelioid sarcoma (ES) is an uncommon soft tissue neoplasm first described in 1970. It is a unique soft tissue neoplasm of adolescents and younger adults which usually presents as a subcutaneous and deep dermal mass in the distal portions of the extremities. The proximal-type variant of this rare soft tissue neoplasm was only recently reported. The proximal form typically arise in proximal extremities and in the deep parts of pelvis, perineum and genital tract. The proximal type variant has distinct histological characteristics and aggressive clinical course as compared to the distal ES. Inactivation of INI1 has been reported in both distal and proximal variants and can help to make the diagnosis. Furthermore, the proximal variant has a possible association with malignant rhabdoid neoplasm. We describe here a case of primary pleural ES of the proximal type and highlight its diagnostic and therapeutic challenges.

7.
Cancers (Basel) ; 11(3)2019 Mar 08.
Article in English | MEDLINE | ID: mdl-30857267

ABSTRACT

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence.

8.
Case Rep Oncol ; 10(3): 998-1005, 2017.
Article in English | MEDLINE | ID: mdl-29279705

ABSTRACT

Solitary fibrous tumor of the pleura is a rare and usually benign primary neoplasm arising from mesenchymal cells of the submesothelial tissue. We present here the case of a patient diagnosed with CD34-positive advanced malignant solitary fibrous tumor of the pleura whose disease failed to respond to combination cytotoxic chemotherapy agents, but demonstrated a prompt near-complete response to checkpoint blockade treatment using the anti-programmed death (PD)-1 monoclonal antibody pembrolizumab, based on tumor molecular profiling revealing tumoral expression positivity for both programmed death-ligand 1 (PD-L1) and PD-1. The patient experienced minimal adverse effects from the treatment with durable favorable response lasting up to cycle 26.

9.
J Clin Pathol ; 70(9): 775-780, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28249941

ABSTRACT

AIMS: To determine the utility of clinical, morphological and phenotypical features in the differential diagnosis of plasmablastic lymphoma and myeloma with plasmablastic features. METHODS: All plasmablastic neoplasms identified from a 15-year retrospective search were reviewed and classified into 'lymphoma', 'myeloma' or 'indeterminate'. The classification was then compared with the previously established clinical diagnosis. Lessons learned from this review were used to design a diagnostic algorithm for pathologists to use in the absence of known clinical history. RESULTS: The classification was possible in 10 of 11 cases, 8 lymphomas and 2 myelomas (n=2). No distinctive morphological or phenotypical features were identified. The most useful histopathological parameter was a positive Epstein-Barr virus in situ hybridisation. Presence of associated lymphadenopathy and/or oral mass in the absence of complete myeloma-defining signs was used to favour a diagnosis of lymphoma in 4 of 8 cases. CONCLUSIONS: The distinction between plasmablastic lymphoma from plasmablastic myeloma warrants detailed knowledge of clinical, radiological and laboratorial findings. New studies identifying distinctive phenotypical or genetic features are needed to improve the histopathological differentiation of plasmablastic neoplasms.


Subject(s)
Multiple Myeloma/diagnosis , Plasmablastic Lymphoma/diagnosis , Adult , Aged , Algorithms , Biomarkers, Tumor/analysis , Biopsy , Decision Support Techniques , Diagnosis, Differential , Diagnostic Errors/prevention & control , Female , Flow Cytometry , Herpesvirus 4, Human/genetics , Humans , Immunohistochemistry , In Situ Hybridization , Male , Middle Aged , Multiple Myeloma/chemistry , Multiple Myeloma/pathology , Multiple Myeloma/virology , Phenotype , Plasmablastic Lymphoma/chemistry , Plasmablastic Lymphoma/pathology , Plasmablastic Lymphoma/virology , Predictive Value of Tests , RNA, Viral/genetics , Retrospective Studies
10.
Mol Cancer Res ; 15(6): 670-682, 2017 06.
Article in English | MEDLINE | ID: mdl-28235899

ABSTRACT

Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility. Mechanistically, NEDD9 promotes mesenchymal migration via VAV2-dependent Rac1 activation, and depletion of VAV2 impairs the ability of NEDD9 to activate Rac1. In addition, NEDD9 supports a mesenchymal phenotype through stimulating polymerization of actin via promoting CTTN phosphorylation in an AURKA-dependent manner. Interestingly, an increase in RhoA activity in NEDD9-depleted cells does not facilitate a switch to functional amoeboid motility, indicating a role of NEDD9 in the regulation of downstream RhoA signaling effectors. Simultaneous depletion of NEDD9 or inhibition of AURKA in combination with inhibition of the amoeboid driver ROCK results in an additional decrease in cancer cell migration/invasion. Finally, we confirmed that a dual targeting strategy is a viable and efficient therapeutic approach to hinder the metastasis of breast cancer in xenograft models, showcasing the important need for further clinical evaluation of this regimen to impede the spread of disease and improve patient survival.Implications: This study provides new insight into the therapeutic benefit of combining NEDD9 depletion with ROCK inhibition to reduce tumor cell dissemination and discovers a new regulatory role of NEDD9 in the modulation of VAV2-dependent activation of Rac1 and actin polymerization. Mol Cancer Res; 15(6); 670-82. ©2017 AACR.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Molecular Targeted Therapy/methods , Phosphoproteins/metabolism , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , rac1 GTP-Binding Protein/metabolism , Adaptor Proteins, Signal Transducing/genetics , Amides/pharmacology , Animals , Aurora Kinase A/metabolism , Azepines/pharmacology , Cell Line, Tumor , Cell Movement , Cortactin/metabolism , Enzyme Inhibitors/pharmacology , Female , Humans , Mice, Inbred NOD , Myosin Light Chains/metabolism , Phosphoproteins/genetics , Phosphorylation , Proto-Oncogene Proteins c-vav/metabolism , Pyridines/pharmacology , Pyrimidines/pharmacology , Triple Negative Breast Neoplasms/metabolism , Xenograft Model Antitumor Assays , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/metabolism
11.
Mol Cancer Ther ; 15(8): 1809-22, 2016 08.
Article in English | MEDLINE | ID: mdl-27235164

ABSTRACT

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule-targeting drug eribulin on different stages of metastasis in triple-negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells, providing foundation for the combination therapy. Mechanistically, AURKA inhibition induces cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but has no effect on growth of mammary tumor. Combination of MLN8237 with eribulin leads to a synergistic increase in apoptosis in mammary tumors, as well as cytotoxic autophagy in metastases. These preclinical data provide a new understanding of the mechanisms by which MLN8237 mediates its antimetastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early-stage solid tumors. Mol Cancer Ther; 15(8); 1809-22. ©2016 AACR.


Subject(s)
Aurora Kinase A/antagonists & inhibitors , Autophagy/drug effects , Azepines/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Furans/pharmacology , Ketones/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Disease Models, Animal , Drug Synergism , Enzyme Activation/drug effects , Female , Humans , Kaplan-Meier Estimate , Male , Neoplasm Metastasis , Signal Transduction/drug effects , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
12.
W V Med J ; 111(5): 40-5, 2015.
Article in English | MEDLINE | ID: mdl-26521535

ABSTRACT

Molecular testing of non-small cell lung carcinomas (NSCLCC) with adenocarcinoma features has become commonplace with the development and use of targeted treatments for these malignancies. Prior to treating these tumors with targeted drug regimens, testing for specific mutations is usually required to determine the potential response of the tumor to the therapeutic agents. This case review describes a patient with lung cancer showing a specific gene mutation who benefitted from targeted treatment. Also reviewed are the current standards of care and trends in the molecular testing of NSCLC with adenocarcinoma features and possible future molecular targets.


Subject(s)
Adenocarcinoma/diagnosis , Lung Neoplasms/diagnosis , Adenocarcinoma/genetics , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Middle Aged , Molecular Diagnostic Techniques/trends , Mutation
13.
Mol Cancer Res ; 12(5): 681-93, 2014 May.
Article in English | MEDLINE | ID: mdl-24574519

ABSTRACT

UNLABELLED: The prometastatic protein NEDD9 (neural precursor cell expressed, developmentally downregulated 9) is highly expressed in many cancers and is required for mesenchymal individual cell migration and progression to the invasive stage. Nevertheless, the molecular mechanisms of NEDD9-driven migration and the downstream targets effecting metastasis are not well defined. In the current study, knockdown of NEDD9 in highly metastatic tumor cells drastically reduces their migratory capacity due to disruption of actin dynamics at the leading edge. Specifically, NEDD9 deficiency leads to a decrease in the persistence and stability of lamellipodial protrusions similar to knockdown of cortactin (CTTN). Mechanistically, it was shown that NEDD9 binds to and regulates acetylation of CTTN in an Aurora A kinase (AURKA)/HDAC6-dependent manner. The knockdown of NEDD9 or AURKA results in an increase in the amount of acetylated CTTN and a decrease in the binding of CTTN to F-actin. Overexpression of the deacetylation mimicking (9KR) mutant of CTTN is sufficient to restore actin dynamics at the leading edge and migration proficiency of the tumor cells. Inhibition of AURKA and HDAC6 activity by alisertib and Tubastatin A in xenograft models of breast cancer leads to a decrease in the number of pulmonary metastases. Collectively, these findings identify CTTN as the key downstream component of NEDD9-driven migration and metastatic phenotypes. IMPLICATIONS: This study provides a mechanistic platform for therapeutic interventions based on AURKA and HDAC6 inhibition for patients with metastatic breast cancer to prevent and/or eradicate metastases.


Subject(s)
Actins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Aurora Kinase A/metabolism , Cortactin/metabolism , Histone Deacetylases/metabolism , Phosphoproteins/metabolism , Acetylation , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Movement/physiology , Female , HEK293 Cells , Heterografts , Histone Deacetylase 6 , Histone Deacetylase Inhibitors/pharmacology , Humans , Male , Mice , Mice, Inbred NOD , Pseudopodia/metabolism , Pseudopodia/pathology , Transfection , Xenograft Model Antitumor Assays
14.
Acta Cytol ; 50(2): 201-4, 2006.
Article in English | MEDLINE | ID: mdl-16610690

ABSTRACT

BACKGROUND: The probability of anaplastic transformation in a differentiated thyroid carcinoma (DTC) is <2%. Admixture of DTC and undifferentiated carcinoma can occasionally be found in thyroidectomy specimens, or the undifferentiated tumor may develop in metastatic foci months or years after removal of the primary tumor. CASE: Anaplastic transformation of a metastatic DTC was diagnosed at autopsy in a 71-year-old female. At the time of her total thyroidectomy for follicular carcinoma, she already had several lung nodules, which diminished in size upon 131I treatment. Five years later the patient developed a new, pleura-based lung mass. The mass extended along the paraspinal soft tissue and involved the kidney. Fine needle aspiration biopsy of the paraspinal mass resulted in a diagnosis of metastatic squamous cell carcinoma. Two months later the patient died. Histologic evaluation of the lung nodules and pleura-based mass revealed areas of follicular carcinoma intermixed with a various patterns of undifferentiated carcinoma. The paraspinal and kidney mass consisted entirely of anaplastic tumor, including areas of squamoid differentiation. CONCLUSION: In patients with a history of DTC who develop a rapidly growing mass elsewhere, a possibility of metastatic DTC with anaplastic transformation must be considered.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma/diagnosis , Kidney Neoplasms/secondary , Lung Neoplasms/secondary , Spinal Neoplasms/secondary , Thyroid Neoplasms/diagnosis , Aged , Biopsy, Fine-Needle/methods , Carcinoma/secondary , Diagnosis, Differential , Disease Progression , Fatal Outcome , Female , Humans , Sensitivity and Specificity
15.
Hum Pathol ; 37(1): 9-15, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16360410

ABSTRACT

Focal adhesion kinase (FAK) is one of the central signaling molecules found at focal adhesion sites, which are specific areas on the cell membrane where cells attach to extracellular matrix proteins. Focal adhesion kinase interacts with multiple signaling and adaptor molecules and effects several signaling pathways. Overexpression of FAK and its substrate c-Src has been implicated in malignant transformation and acquisition of an invasive tumor phenotype of different tissues. Overexpression of the multidomain protein paxillin, which is also a FAK ligand and a c-Src substrate, has been associated with less malignant tumor behavior. The purpose of this study was to analyze the involvement of integrin signaling molecules FAK, c-Src, and paxillin in malignant transformation of the breast epithelium. Using phosphospecific antibodies FAK-pY(397) and Src-pY(416), we demonstrated that neither activation of FAK nor activation of c-Src correlates with development of invasive tumor properties. However, activation of both FAK and c-Src correlates with malignant transformation. We further demonstrated that overexpression of paxillin also correlates with malignant transformation and is a marker of a less invasive tumor phenotype. Using tissue microarray, we demonstrated that expression and activation of paxillin inversely correlated with lymph node metastases and lymphovascular invasion, respectively. No correlation between paxillin expression and activation and tumor grade, estrogen, progesterone, and Her2/Neu receptor expression was found. In summary, focal adhesion proteins FAK and c-Src can be used as markers of malignant transformation in epithelial cells but not invasive phenotype, whereas expression and activation of paxillin may represent a good prognosticator in breast carcinoma.


Subject(s)
Breast Neoplasms/enzymology , Carcinoma, Ductal, Breast/enzymology , Carcinoma, Intraductal, Noninfiltrating/enzymology , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Paxillin/metabolism , Proto-Oncogene Proteins pp60(c-src)/metabolism , Biomarkers, Tumor/metabolism , Breast/enzymology , Breast/pathology , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Carcinoma, Intraductal, Noninfiltrating/pathology , Cell Transformation, Neoplastic , Female , Fibroadenoma/enzymology , Fibroadenoma/pathology , Humans , Immunohistochemistry , Lymph Nodes/pathology , Prognosis , Protein Array Analysis , Signal Transduction
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