Viktor Goncharuk

Albany Medical College, Albany, New York, United States

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Publications (13)15.08 Total impact

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    ABSTRACT: Matrix metalloproteinases (MMP's) 3, 10 and 11 (also known as stromelysins 1, 2 and 3, respectively), and matrix metalloproteinase 7 (also known as matrilysin), produced by stromal fibroblast-like cells in the vicinity of various malignancies, are suspected to have an ability to degrade components of extracellular matrix, thus promoting spread of the tumor. MMP's also have been found in epithelial tumor cells in various cancers. Tissue sections from 95 cases of non-small cell lung cancer (NSCLC) were immunostained with antibodies against MMP 3, MMP 10 and MMP 11 and sections from 99 cases of NSCLC were immunostained with an antibody against MMP 7. Cytoplasmic immunoreactivity in the tumor cells was semiquantitatively scored for intensity and distribution and correlated with tumor type, tumor grade, stage, tumor size, lymph node positivity, metastasis and survival. Overexpression of MMP 10 and MMP 11 correlated with higher grade for NSCLC (p = 0.029 and p = 0.016, respectively), and also in a subset of adenocarcinomas (AC) (p = 0.015 and p = 0.009, respectively). Also, MMP 10 and MMP 11 correlated with lymph node involvement in NSCLC (p = 0.025 and p = 0.027 respectively). No correlation was found for MMP 3. Overexpression of MMP-7 correlated with tumor stage (p = 0.0001) and was associated with adverse clinical outcome (p = 0.0001) in NSCLC and also in separate squamous cell carcinoma (SCC) (p = 0.003) and AC (p = 0.004) tumor groups.
    Ceskoslovenska patologie 02/2006; 42(1):16-9.
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    Acta Cytologica - ACTA CYTOL. 01/2005; 49:441-444.
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    ABSTRACT: Chyothorax is an uncommon medical condition. To the best of our knowledge, there have been no detailed English-language report dealing with its cytopathologic findings and diagnostic pitfalls A 12-year-old boy, hemodialysis dependent, with congenital nephrotic syndrome due to focal segmental glomerular sclerosis and a failed renal transplant, developed shortness of breath. Physical and radiologic examinations revealed a left pleural effusion. A 7-year-old boy developed shortness of breath, with a subsequent finding of a left pleural effusion. Multiple osteolytic skeletal lesions were found in this patient. Both patients underwent thoracocentesis. Cytologically, both fluids contained many relatively uniform, large lymphoid cells with high nuclear/cytoplasmic (N/C) ratio, condensed chromatin and occasional nucleoli, resembling blasts. Some nuclei were convoluted. Mitotic figures were present. Foamy macrophages were present in both cases. The differential diagnosis of these populations of cells included a lymphoproliferative disorder. However, the mature T-lymphocytic nature of the cells was confirmed by immunohistochemistry performed on cell block preparations, confirming the clinical impression of chylothorax in both cases. The first patient had chylothorax as a result of trauma due to therapeutic interventions (subclavian vein cannulation), in the second patient the chylothorax was a part of Gorham-Stout syndrome. The large T-lymphocytes that are the major cellular component of chylothorax may arouse suspicion of a lymphoproliferative disorder. Attention to the clinical history and immunophenotyping confirm the benign nature of the pleural space fluid. Also, abundant foamy macrophages can be considered a low-power clue to this diagnosis.
    Acta cytologica 01/2005; 49(4):441-4. · 0.69 Impact Factor
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    ABSTRACT: Inhibitors of apoptosis, including bcl-2 and survivin (a novel gene encoding a unique apoptosis inhibitor), regulate cell proliferation by promoting cell survival. Although survivin has been detected in several human cancers, its prognostic significance and relationship to bcl-2 are not well characterized in lung cancer. Tissue sections from 102 non-small cell lung carcinomas (NSCLC) were immunostained using antibodies against survivin and bcl-2. Staining results were correlated with prognostic variables. Immunoreactivity for survivin and bcl-2 was observed in 53% and 21% of NSCLCs, respectively. Fifty-two percent of the 50 squamous cell carcinomas and 54% of the 52 adenocarcinomas expressed survivin. Survivin positivity correlated with tumor stage in squamous cell carcinoma. On univariate analysis, survivin expression correlated with decreased patient survival in NSCLC and in the subset of squamous cell carcinomas, but not in adenocarcinomas. On multivariate analysis, survivin was an independent predictor, along with distant metastasis and large tumor size. Eighteen percent of squamous cell carcinomas and 24% of adenocarcinomas expressed bcl-2. On univariate analysis, bcl-2 expression correlated with increased patient survival in NSCLC and in the subset of squamous cell carcinomas. An inverse correlation between the expression of survivin and bcl-2 was noted. Survivin immunoreactivity is an independent predictor of shortened survival in NSCLC, while bcl-2 protein expression correlated with prolonged patient survival. These findings indicate an inverse relationship between survivin and bcl-2 expression and suggest that these two inhibitors of apoptosis function through different pathways in the regulation of tumorigenesis in NSCLC.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 04/2004; 12(1):44-9. · 1.63 Impact Factor
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    ABSTRACT: The multistep process of carcinogenesis implies the accumulation of multiple molecular defects. Alteration of tumor suppressor and metastasis suppressor genes are the important steps. Increasing experimental evidence indicates that decreased expression of tumor-metastasis/suppressor genes and gene products are involved in the progression of a variety of human malignancies. In the present study, we have extended this analysis to non-small cell lung carcinomas (NSCLC). The expression and prognostic significance of the tumor suppressor gene PTEN and metastasis suppressor genes nm23-H1 and KAI-1 was evaluated in NSCLCs. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissues from 53 bronchogenic adenocarcinomas and 51 squamous cell carcinomas using monoclonal antibodies against PTEN, nm23H-1, and KAI-1 proteins. Immunohistochemical results were correlated with tumor stage, grade, lymph nodes positivity, metastasis, and patient survival. Significant co-expression of PTEN, nm23-H1 and KAI-1 was observed in NSCLC (P<.001 to .002). The immunohistochemical expression of these proteins was significantly higher in stages 1 and 2 compared with stages 3 and 4 (P=.04 for PTEN and KAI-1, P=.039 for nm23-H1). When all stages were considered together, loss of immunoreactivity for PTEN, nm23-H1 and KAI-1 was found in advanced NCSCLs (P=.015 for PTEN, P=.001 for KAI-1, P=.004 for nm23-H1), which is suggestive of co-downregulation of these proteins in the process of tumor progression. On multivariate analysis, negative staining for PTEN (P=.014), KAI-1 (P=.034), and nm23-H1 (a trend toward association for nm23-H1 reached near significance P=.08) correlated with disease-related death. Positive lymph node status was associated with negative immunostaining for PTEN (P=.007) but no correlation was observed for nm23-H1 and KAI-1. Loss of expression was linked to distant metastasis (P=.006 for PTEN, P=.002 for nm23H1, P=.001 for KAI-1). On multivariate analysis, co-downregulation of PTEN (P=.009), KAI-1 (P=.02), and nm23-H1 (P=.011) independently predicted shortened survival in NSCLC. Although NSCLC exhibits strong co-expression of PTEN, nm23-H1 and KAI-1, there is a loss of these proteins in high-stage tumors. Co-downregulation of PTEN, KAI-1, and nm23-H1 significantly correlates with distant metastasis and predicts shortened survival. Our study supports a role of these tumor suppressor and metastasis suppressor genes in the evolution and progression of NSCLC.
    Annals of Diagnostic Pathology 03/2004; 8(1):6-16. · 0.98 Impact Factor
  • Medical and Pediatric Oncology 07/2003; 40(6):411-2.
  • Archives of Dermatology 05/2003; 139(4):542-3. · 4.79 Impact Factor
  • Viktor Goncharuk, Michael Mulvaney, J Andrew Carlson
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    ABSTRACT: Neuroectodermal differentiation or melanocytic colonization are the opposing theories of histogenesis for the Bednár tumor or pigmented dermatofibrosarcoma protuberans (DFSP). A 31-year-old African-American woman presented with a 2-cm blue-black shoulder nodule of 1-year duration. Punch biopsy revealed a CD34+, Factor XIIIa-DFSP, harboring numerous, pigmented spindle S100+, Mart-1+ and HMB-45+ cells. Subsequent wide excision demonstrated pigmented dendritic and spindled cells widely scattered throughout the dermis of the 3-cm excisional margins and punch biopsy specimens of normal skin from both shoulders. This latter process was interpreted as dermal melanocytosis (nevus of Ito). The dermal pigmented spindle cells were Mart-1+ and CD34-, and were associated with non-pigmented CD34+, cytologically banal spindle cells, which were more numerous in the excisional margins than the contralateral shoulder. Reported herein is a singular case of Bednár tumor associated with dermal melanocytosis. Although the coexistence of these processes implicates colonization of the DFSP by constituent dermal melanocytes, the mixed immunophenotype (CD34+ or Mart-1+ cells) of dispersed dermal spindle cells hints at the possibility of a common cell of origin: the putative neuromesenchymal cell. In effect, the Bednár tumor could represent one part of a spectrum of neural crest-derived dermal tumors that includes dermal melanocytosis, cellular blue nevus and conventional DFSP.
    Journal of Cutaneous Pathology 03/2003; 30(2):147-51. · 1.77 Impact Factor
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    ABSTRACT: A case of botryoid-type embryonal rhabdomyosarcoma of the renal pelvis in a 49-year-old woman is reported. The tumor led to hydronephrosis. The surgical resection specimen disclosed a translucent, polypoid mass attached to the wall of the renal pelvis by thin stalk. Light-microscopic examination revealed a large exophytic polypoid tumor with intact surface epithelium, which was negative for dysplasia or carcinoma in situ. There was a condensation of epithelioid to spindle cells underneath the basement membrane, forming a cambium layer. The core of the lesion contained interspersed epithelioid to spindle cells with myxoid change and edema. Cells of the cambium layer as well as interspersed cells in the core exhibited marked cytologic atypia with mitotic figures. Immunohistochemical stains for cytokeratin, S-100 and myoglobin were negative, stains for desmin and actin were positive. Although botryoid-type embryonal rhabdomyosarcomas have been reported to occur at various sites in the genital tract and lower urinary tract, to our knowledge, this is the first reported case of the tumor within the renal pelvis. Also, the occurrence of these tumors in adults is quite rare.
    Ceskoslovenska patologie 02/2003; 39(1):31-5.
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    ABSTRACT: The E-cadherin-catenin complex proteins function in cell-cell adhesion and have been reported to be dysregulated in various human malignancies. Beta catenin is a cytoplasmic protein that associates with tyrosine kinase receptors and modulates cytoskeletal dynamics. It also plays a role in the Wnt signaling pathway. During neoplastic transformation, the phosphorylation of beta-catenin causes a loss of intercellular adhesions resulting in increased tumor cell motility and invasiveness. Tissue sections from 100 cases of non-small cell lung cancer (NSCLC) were immunostained with a monoclonal beta-catenin antibody. There were 47 squamous cell carcinomas (SCC) and 53 adenocarcinomas (AC) in the study group. Plasma membrane/cytoplasmic beta-catenin immunoreactivity was scored for intensity and distribution and correlated with tumor stage, grade and survival. Plasma membrane/cytoplasmic immunoreactivity for beta-catenin protein was observed in 71 (71%) of 100 NSCLC. 44 (94%) of 47 SCC and 27 (51%) of 53 AC expressed beta catenin. On univariate analysis, loss of beta catenin expression correlated with high tumor stage (p = 0.025), large tumor size (p = 0.02) and decreased patient survival (p = 0.04). The loss of beta catenin expression associated with high grade NSCLC reached near significance (p = 0.07). On multivariate analysis, the loss of beta catenin expression independently predicted shortened overall patient survival in NSCLC (p = 0.05). Beta catenin expression loss is associated with advanced tumor stage and is an independent predictor of shortened patient survival in NSCLC.
    Ceskoslovenska patologie 02/2003; 39(1):17-20.
  • Viktor N Goncharuk, Jeffrey S Ross, J Andrew Carlson
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    ABSTRACT: Fascin containing actin bundles provide mechanical support to cellular protrusions and stress fibers. In cancers, some malignant cells (e.g. subsets of breast and ovarian carcinomas) express fascin. In skin cancer, the role of fascin is unknown. Cases of 61 keratocytic neoplasms, 35 melanocytic neoplasms, nine extramammary Paget's disease (four with adenocarcinoma) and five sarcomas (angiosarcoma and atypical fibroxanthoma) were examined by immunohistochemistry, using monoclonal antihuman fascin antibody, clone 55 k-2 (Dako Corporation, Carpinteria, CA, USA). Fascin labeled all sarcomas and all keratinocytic neoplasms except for pagetoid pattern Bowen's disease. The regions of most intense fascin labeling were seen in the basal cells of infiltrative tumor margins. A minority of Merkel cell carcinomas exhibited weak or absent immunoreactivity. All melanocytic nevi except for some junctional nests of dysplastic melanocytic nevi expressed fascin. However, pagetoid cells of melanoma in situ and epithelioid cells of invasive melanoma weakly expressed or did not express fascin, whereas melanoma cells exhibiting spindle cell morphologies labeled intensely with fascin. Lastly, all cells of extramammary Paget's disease and most associated adenocarcinomas cells did not or were faintly labeled by fascin antibodies. Decreased or absent fascin expression was significantly associated with skin cancers with a high risk for metastasis (e.g. melanoma) vs. those with a low risk (e.g. basal cell carcinoma) (24% vs. 100% with > 50% immunoreactivity; p = 0.0001, chi-squared test). Fascin is expressed by skin tumors that locally infiltrate and replace surrounding tissues indicating a role for fascin in cell adhesion, cell motility and invasiveness. No or weak fascin expression is exhibited by cancers with pagetoid intraepidermal spread and by invasive tumors with a high risk of metastasis. Downregulation or loss of fascin's actin-bundling properties, probably associated with disorganization of cell-cell and cell-matrix contacts, may be a crucial step in the progression from locally invasive to widely disseminating cancers.
    Journal of Cutaneous Pathology 08/2002; 29(7):430-8. · 1.77 Impact Factor
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    ABSTRACT: To determine if carcinogenic events in vulvar skin precede the onset of morphologic atypia, the authors investigated for derangements in DNA content, cell proliferation, and cell death in vulvar carcinomas and surrounding skin in 140 samples of tumor and surrounding skin collected from 35 consecutive vulvectomy specimen for squamous cell carcinoma (SCC) or vulvar intraepithelial neoplasia (VIN) 3. Vulvar non-cancer excisions were used as controls. Investigations consisted of histologic classification and measurement of 9 variables--epidermal thickness (acanthosis and rete ridge length), immunolabeling index (LI) for 3 proteins (p53 protein, Ki-67, and mdm-2), pattern of p53 expression (dispersed vs. compact), DNA content index, and presence of aneuploidy by image analysis and apoptotic rate by Apotag labeling. Significant positive correlations were found for all nine variables studied versus increasing histologic severity in two proposed histologic stepwise models of vulvar carcinogenesis (lichen sclerosus (LS) and VIN 3 undifferentiated associated SCC groups). High p53 LI (>25) and the compact pattern of p53 expression (suspected oncoprotein) significantly correlated with LS and its associated vulvar samples compared with samples not associated with LS (P < or = 0.001). Furthermore, p53 LI, mdm-2 LI, and pattern of p53 expression were concordant between patient matched samples of LS and SCC. In addition, mdm-2 LI significantly correlated with dispersed pattern p53 LI suggesting a response to wild-type p53 protein accumulation. These findings support the hypothesis that neoplastic transformation occurs in sequential steps and compromises proteins involved in the cell cycle control. Concordance of p53 and mdm-2 protein expression in LS and adjacent SCC provides evidence that LS can act as a precursor lesion in the absence of morphologic atypia. Overexpression of mdm-2 with stabilization and inactivation of p53 protein may provide an alternate pathway for vulvar carcinogenesis.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 06/2001; 9(2):150-63. · 1.63 Impact Factor
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    ABSTRACT: To determine if carcinogenic events in vulvar skin precede the onset of morphologic atypia, the authors investigated for derangements in DNA content, cell proliferation, and cell death in vulvar carcinomas and surrounding skin in 140 samples of tumor and surrounding skin collected from 35 consecutive vulvectomy specimen for squamous cell carcinoma (SCC) or vulvar intraepithelial neoplasia (VIN) 3. Vulvar non-cancer excisions were used as controls. Investigations consisted of histologic classification and measurement of 9 variables—epidermal thickness (acanthosis and rete ridge length), immunolabeling index (LI) for 3 proteins (p53 protein, Ki-67, and mdm-2), pattern of p53 expression (dispersed vs. compact), DNA content index, and presence of aneuploidy by image analysis and apoptotic rate by Apotag labeling. Significant positive correlations were found for all nine variables studied versus increasing histologic severity in two proposed histologic stepwise models of vulvar carcinogenesis (lichen sclerosus (LS) and VIN 3 undifferentiated associated SCC groups). High p53 LI (>25) and the compact pattern of p53 expression (suspected oncoprotein) significantly correlated with LS and its associated vulvar samples compared with samples not associated with LS (P ≤ 0.001). Furthermore, p53 LI, mdm-2 LI, and pattern of p53 expression were concordant between patient matched samples of LS and SCC. In addition, mdm-2 LI significantly correlated with dispersed pattern p53 LI suggesting a response to wild-type p53 protein accumulation. These findings support the hypothesis that neoplastic transformation occurs in sequential steps and compromises proteins involved in the cell cycle control. Concordance of p53 and mdm-2 protein expression in LS and adjacent SCC provides evidence that LS can act as a precursor lesion in the absence of morphologic atypia. Overexpression of mdm-2 with stabilization and inactivation of p53 protein may provide an alternate pathway for vulvar carcinogenesis. Vulvar squamous cell carcinoma (SCC) is a rare cancer whose incidence increases progressively with age. Risk factors for vulvar carcinoma include other genital carcinomas, chronic vulvar inflammatory disorders, smoking, genital warts, and vulvar intraepithelial neoplasia (VIN) (1–5). Histopathologic, molecular, and epidemiologic studies have revealed two subsets of vulvar SCCs: 1) younger women with human papillomavirus (HPV) risk factors, and 2) older women without HPV risk factors who are commonly affected by vulvar lichen sclerosus (LS) (6,7). It is suspected that the pathway to human papillomavirus positive and negative vulvar SCCs may involve not only obvious precancerous changes, e.g., VIN 3 (a.k.a. squamous cell carcinoma in situ), but also biologic events in the vulvar mucosa that precede the onset of morphologic atypia (6–8). Possible precursor lesions without morphologic atypia could include LS or “squamous hyperplasia” (a.k.a. lichen simplex chronicus), or both. Squamous hyperplasia (epidermal proliferation characterized by increasing epidermal thickness) has been implicated as a precursor lesion in the development of vulvar SCC (9,10). However, the term “squamous hyperplasia” is poorly defined (11) and most often represents the clinicopathologic entity lichen simplex chronicus—a disorder that responds to antiinflammatory (topical corticosteroid) treatments as expected for an inflammatory dermatosis (12). In the current study, rather than simply examining the role of squamous hyperplasia in vulvar neoplasia in terms of histologic classification, the authors examined the measurable elements of squamous hyperplasia—acanthosis and rete ridge length—and compared these characteristics with markers of neoplastic progression and across histologic categories. Mutation of p53 tumor suppressor gene is implicated in vulvar carcinogenesis (7,9,13–17) and is frequently heralded by accumulation of p53 oncoprotein that is more stable than wild-type protein (18). Recently, discrete zones of keratinocytes intensely stained by antibodies to p53 protein, the so-called “compact band,” have been found after microdissection and DNA sequencing to reflect clonal multiplication of keratinocytes with mutated p53 gene (19). The finding of p53 protein overexpression (or absence of) in the form of compact bands of p53 labeling in vulvar SCCs and synchronous skin could identify precursor lesions and indicate how early p53 gene mutation occurs in vulvar carcinogenesis. The mdm-2 protein inhibits the G1 arrest and apoptosis functions of p53 protein (20). Through inactivation of wild-type p53 protein, mdm-2 overexpression could provide an alternate pathway to p53 mutation in neoplastic progression (21). Therefore, mdm-2 expression possibly could be involved in some cases of vulvar neoplasia (correlate to p53 expression or other cell cycle factors), or vulvar neoplastic progression, or both. Ki-67 (MIB-1) is a cell cycle antigen expressed throughout all active stages of the cell cycle (G1, S, G2, and M) (22) and has been found to be elevated in vulvar SCCs and their adjacent skin (7,23–27). As carcinomas are proliferative disorders characterized by uncoordinated cell growth (28,29), the growth fraction (percent of cells expressing Ki-67) would be expected to increase with increasing histologic severity. Apoptosis (programed cell death), out of balance with cell proliferation, may play a part in carcinogenesis (30). The exact role apoptosis plays in the progression from normal to malignant tissue is unknown and current data is contradictory as either high cell turnover states (high apoptosis) or high population expansion states (high mitosis) can be evident. For example, oral SCCs show a lower apoptotic index than high grade squamous dysplasia (31), whereas gastric adenocarcinomas demonstrate increased rates of apoptosis compared with gastric adenomas (32). Alterations of apoptosis have not been extensively studied for vulvar carcinogenesis (33,34). Chromosomal instability (aneuploidy) is found in most human tumors (35) and may be the consequence of a mutated chromosome-segregation gene (29) or the presence of aneuploidy (36,37). DNA aneuploidy frequently is identified in vulvar SCCs (7,8,38). Thus, abnormalities in DNA content would be expected to be found in precursor lesions of vulvar SCC. The “field cancerization” theory states that all of the epithelium of the upper aerodigestive tract has been mutagenized, presumably as a result of exposure to carcinogens such as tobacco smoke, and therefore, is at increased risk for multiple epithelial tumors (39,40). This theory may apply equally to women affected by vulvar SCC as they are at high risk for second primary SCCs (3,7,41). According to this theory, the vulvar epithelium has been subjected to mutagens (e.g., oncogenic HPVs and or free radicals from persistent inflammation), has become initiated, and therefore is at risk for one or more cancers (6,7,42). To investigate the theory of field cancerization in the vulva and to identify precursor lesions without morphologic atypia, the authors studied the above described factors related to cell proliferation, cell death, and DNA content in vulvar cancers and their adjacent skin. Also, if development of SCC of the vulva is a multistep process resulting from an accumulation of defects in cell proliferation, cell death, and DNA content, one would expect to observe an incremental increase in the frequency of these alterations with neoplastic progression. To test this hypothesis, the authors applied stepwise histologic models to the two subsets of vulvar cancer (LS and VIN 3 undifferentiated associated SCC) to determine whether the neoplastic markers examined in the current study could be linked with histologic progression to cancer.
    Applied Immunohistochemistry 05/2001; 9(2):150-163. · 1.83 Impact Factor