Terrence M Katona

State University of New York Downstate Medical Center, Brooklyn, New York, United States

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Publications (11)36.26 Total impact

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    ABSTRACT: BACKGROUND:: Mycosis fungoides (MF) exhibits a variety of underlying molecular defects including aberrations involving the PTEN tumor suppressor gene. Specifically, loss of heterozygosity of PTEN has been previously demonstrated. We hypothesize that abnormalities of PTEN may result in altered immunohistochemical expression of its protein product. METHODS:: Thirty-six MF specimens were stained with monoclonal antibody against PTEN protein. The percentage of nuclei retaining PTEN expression and the staining intensity was recorded. RESULTS:: Average percentage of lymphoma cells retaining expression of the PTEN protein was 92% within patch-stage lesions, 81.4% in plaque-stage lesions, and 81.1% in tumor-stage lesions. Average intensity of staining for patch-stage lesions was 2.90, 2.50 for plaque lesions and 2.44 for tumor lesions. Cases lacking loss of heterozygozity at PTEN (n = 6) had an average expression of 81% and an average intensity of staining of 2.42. Whereas, cases with loss of heterozygozity at PTEN (n = 6) had an average expression of 75% of cells with an average staining intensity of 2.33. CONCLUSIONS:: The percentage of cells retaining PTEN and staining intensity decrease from patch- to plaque-stage lesions, whereas both parameters show mild diminution in tumor lesions compared with plaque lesions. PTEN expression in a small sample seems to correlate with previous demonstration of loss of heterozygosity at the molecular level. Although a trend for loss of PTEN expression exists with histologic progression of MF, the effect is modest and may not represent the pivotal defect in MF pathogenesis.
    The American Journal of dermatopathology 05/2013; · 1.30 Impact Factor
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    ABSTRACT: We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.
    Prostaglandins Leukotrienes and Essential Fatty Acids 08/2009; 81(4):279-90. · 2.73 Impact Factor
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    Terrence M Katona, Susan M Perkins, Steven D Billings
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    ABSTRACT: Evaluation of androgen receptor (AR) and cytokeratin 20 (CK20) expression can aid in distinguishing between conventional basal cell carcinoma (characteristically AR+, CK20-) and trichoepithelioma (frequently AR-, CK20+). Within these two groups of tumors, morpheaform/infiltrative basal cell carcinoma (mBCC) and desmoplastic trichoepithelioma (DTE) are particularly challenging to differentiate both clinically and histologically. We investigated whether AR and CK20 immunostains may distinguish between mBCC and DTE. Immunohistochemistry for AR and CK20 was performed on 15 DTEs and 31 mBCCs. Any immunoreactivity within the tumor for AR or CK20 was considered positive. AR expression was seen in 13% (2/15) of DTE and 65% (20/31) of mBCC cases (chi-square p = 0.0011). CK20-positive Mërkel cells were identified in 100% (15/15) of DTE and 3% (1/31) of mBCC (chi-square p < 0.0001). The expected pattern of AR-, CK20+ immunophenotype was present in 87% (13/15) of DTE cases. In mBCC, 61% (19/31) was AR+, CK20-. No DTE was AR+, CK20- and no mBCC was AR-, CK20+. Immunohistochemical stains for AR and CK20 are useful to differentiate DTE from mBCC. The AR-, CK20+ immunophenotype is sensitive (87%) and specific for DTE (100%). The AR+, CK20- immunophenotype is specific (100%) and moderately sensitive (61%) for mBCC.
    Journal of Cutaneous Pathology 02/2008; 35(2):174-9. · 1.77 Impact Factor
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    ABSTRACT: The OCT4 transcription factor is a marker of pluripotency and is present in embryonic stem cells, primordial germ cells, and several neoplasms including seminoma, dysgerminoma, and embryonal carcinoma. Recently, immunohistochemical expression of OCT4 protein has been described in the cells within the basal layer of normal human and canine epidermis. We have examined a series of basal cell carcinomas and adnexal tumors of related histogenesis, in an effort to corroborate the above findings and to assess for expression of OCT4 protein in neoplasia of the infundibulo-apocrine-sebaceous unit. We analyzed OCT4 expression in 115 cutaneous specimens including 26 basal cell carcinomas, 12 benign follicular tumors (10 trichoepitheliomas and 2 trichoblastomas), 10 benign apocrine tumors, 12 sebaceous hyperplasia lesions, 10 sebaceous adenomas, 4 sebaceous carcinomas, 13 nevi sebacei of Jadassohn, 8 squamous cell carcinomas (including one spindle-cell squamous cell carcinoma), 8 compound melanocytic nevi, 5 Merkel cell carcinomas, 3 pilar cysts, 1 scar, 2 nonspecific, mild superficial perivascular dermatitis specimens, and 1 non-scarring alopecia. All 115 specimens examined were negative for OCT4 expression as was adjacent or overlying epidermis and follicular epithelium including the bulge region. In contrast to previous studies, our data indicate that the OCT4 expression is not retained in cutaneous neoplasms derived from basal epidermis or related adnexal neoplasms, including lesions of the scalp.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 01/2008; 15(4):359-62. · 1.63 Impact Factor
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    ABSTRACT: Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64%) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47%) plaque and in 9 of 10 (90%) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70%) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.
    American Journal of Surgical Pathology 11/2007; 31(10):1552-6. · 4.87 Impact Factor
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    ABSTRACT: Melanoma of the skin frequently metastasizes to multiple regional lymph nodes and to distant sites. It is uncertain whether all metastases originate from the same tumor clone or whether the genetic heterogeneity of the primary tumor is reflected in the multiple metastases. A total of 73 archival, formalin-fixed, paraffin-embedded, melanoma lesions, including 13 primary tumors and 60 metastases, were studied from 13 patients each having 2 or more metastatic tumors. Genomic DNA samples were prepared from tissue sections using laser-assisted microdissection. We find that the majority of melanoma metastases share a common clonal origin with the matched primary tumor. However, significant genetic divergence occurs frequently during the clonal evolution of metastatic melanoma. In addition, using X-chromosome inactivation analysis, we find that, in some cases, multiple coexisting metastases seem to be derived from different, genetically unrelated tumor clones, implying that some primary tumors may arise from more than a single transformed melanocyte.
    American Journal of Surgical Pathology 08/2007; 31(7):1029-37. · 4.87 Impact Factor
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    ABSTRACT: The classification of fibroepithelioma of Pinkus as basal cell carcinoma or trichoblastoma remains controversial. Immunohistochemical stains for androgen receptor may be useful in differentiating basal cell carcinoma from trichoepithelioma or trichoblastoma. We studied androgen receptor expression in 13 fibroepitheliomas of Pinkus, 11 basal cell carcinomas, 12 trichoepitheliomas, and 3 trichoblastomas. Androgen receptor expression was present in 77% (10/13) of fibroepitheliomas of Pinkus, 73% (8/11) of basal cell carcinomas, 17% (2/12) of trichoepitheliomas, and 0% (0/3) of trichoblastomas. Androgen receptor expression was significantly higher in fibroepitheliomas of Pinkus compared with trichoepitheliomas and trichoblastomas (P = .0007), but not basal cell carcinoma (P = 1.00). Tumor-associated Merkel cells, a feature of benign follicular tumors, was identified by cytokeratin 20 stains. Merkel cells were identified in 85% (11/13) of fibroepitheliomas of Pinkus, 27% (3/11) of basal cell carcinoma cases, and 73% (11/15) of benign follicular tumors. Cytokeratin 20 expression was significantly higher in fibroepithelioma of Pinkus and benign follicular tumors compared with basal cell carcinomas (P = 0.0111 and P = 0.025, respectively). No significant difference was found between fibroepitheliomas of Pinkus and trichoepitheliomas and trichoblastomas (P = 1.00). Similar to basal cell carcinomas, fibroepitheliomas of Pinkus express androgen receptors, potentially supporting classification as a basal cell carcinoma. Conversely, fibroepithelioma of Pinkus demonstrates retention of Merkel cells, a feature of benign follicular tumors. Immunophenotypic evidence for the classification of fibroepithelioma of Pinkus remains inconclusive. In small, partial biopsy specimens, coexpression of androgen receptor and cytokeratin 20 may aid in the diagnosis of fibroepithelioma of Pinkus.
    American Journal of Dermatopathology 03/2007; 29(1):7-12. · 1.42 Impact Factor
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    ABSTRACT: Penile soft tissue tumors comprise 5% of tumors at this site and most have been reported as isolated case reports. The purpose of this review is to aid the practicing surgical pathologist in distinguishing penile soft tissue tumors, such as sarcomatoid squamous cell carcinoma, from other prognostically and therapeutically important entities in the differential diagnosis. Clinical presentation, management, prognosis and factors influencing behavior are reviewed. The immunohistochemical profiles and salient morphologic clues that may help distinguish penile spindle cell tumors from sarcomatoid carcinomas are evaluated. Soft tissue tumors of the penis may be classified as benign or malignant, as superficial or deep and in terms of age at presentation. All are rare. The most common benign soft tissue tumors that affect the penis are vascular neoplasms, followed by tumors of neural, myoid and fibrous origin. Among reported cases, the most frequent malignant penile soft tissue tumors are Kaposi sarcoma and leiomyosarcoma. Correctly diagnosing penile soft tissue tumors is imperative, because the biologic behavior and the clinical management of these neoplasms vary considerably. Distinguishing sarcomas from sarcomatoid carcinoma and melanoma is particularly important. Accurate diagnosis is best facilitated by consideration of all available aspects of the case, including clinical information, histopathologic findings and immunohistochemical results.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 09/2006; 28(4):193-206. · 0.60 Impact Factor
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    ABSTRACT: Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92%) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis.
    Cancer Research 06/2006; 66(9):4936-42. · 8.65 Impact Factor
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    ABSTRACT: Malignant fibrous histiocytoma has been regarded as the most common sarcoma of older adults. However, recent opinion regards pleomorphic malignant fibrous histiocytoma as an undifferentiated high grade pleomorphic sarcoma not otherwise classifiable utilizing current techniques available in surgical pathology. Notwithstanding controversy regarding its nomenclature, malignant fibrous histiocytoma involving the penis is exceedingly rare, with only 4 cases previously described, to our knowledge. An uncircumcised 73-year-old male presented with a painless, granular, partially necrotic lesion beneath the penile foreskin. There was no history of sexually transmitted disease, constitutional symptoms or dysuria. Examination of penile shaft, testicles, spermatic cord and inguinal lymph nodes were unremarkable. Biopsy revealed a markedly pleomorphic sarcoma. Subsequent, partial penectomy revealed the same lesion with an adjacent area of squamous cell carcinoma in situ. Malignant fibrous histiocytoma remains a diagnosis of exclusion. The investigation requires extensive tumor sampling in search of areas of differentiation and a complete battery of immunohistochemical markers. Therapeutically important entities in the differential diagnosis that must be ruled out include other poorly differentiated sarcomas, sarcomatoid squamous cell carcinoma and desmoplastic melanoma.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 03/2006; 28(1):39-42. · 0.60 Impact Factor
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    ABSTRACT: Angiogenin is a polypeptide involved in the formation and establishment of new blood vessels necessary for growth and metastasis of numerous malignant neoplasms, including prostatic adenocarcinoma. Antiangiogenin therapy inhibits the establishment, growth, and metastasis of prostatic adenocarcinoma in animal studies. In this study, we have investigated the expression of angiogenin in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostatic epithelium in a large cohort of prostatectomy specimens. We have studied the expression of angiogenin by immunohistochemistry in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostatic tissue in 107 human total prostatectomy specimens. The percentage of cells staining positively for angiogenin in benign prostatic glandular epithelium (mean = 17%) was significantly less than for high-grade prostatic intraepithelial neoplasia (mean = 58%, P < 0.001) and prostatic adenocarcinoma (mean = 60%, P < 0.001). Compared with adjacent benign prostatic epithelium, the staining intensity was significantly greater in high-grade prostatic intraepithelial neoplasia (P < 0.001) and prostatic adenocarcinoma (P < 0.001). Furthermore, staining intensity has significantly stronger in prostatic adenocarcinoma versus high-grade prostatic intraepithelial neoplasia (P = 0.0023). However, there was no correlation of angiogenin expression with various clinical and pathologic variables examined, including age at surgery, Gleason scores, pathologic stage, tumor extent, angiolymphatic invasion, extraprostatic extension, seminal vesical invasion, lymph node metastasis, surgical margin status, presence of prostatic intraepithelial neoplasia, and perineural invasion. Angiogenin expression in prostatic tissue increases as prostatic epithelial cells evolve from a benign to an invasive phenotype. The increasing expression of prostatic adenocarcinoma in the progression from benign prostate to high-grade prostatic intraepithelial neoplasia and ultimately to prostatic adenocarcinoma are consistent with previous studies showing the influential role that angiogenin plays in the growth, invasion, and metastasis of prostatic adenocarcinoma and many other malignant tumors.
    Clinical Cancer Research 12/2005; 11(23):8358-63. · 7.84 Impact Factor

Publication Stats

133 Citations
36.26 Total Impact Points

Institutions

  • 2013
    • State University of New York Downstate Medical Center
      Brooklyn, New York, United States
  • 2006–2008
    • Indiana University-Purdue University Indianapolis
      • Department of Pathology and Laboratory Medicine
      Indianapolis, IN, United States