Retrospective Study of 338 Canine Oral Melanomas with Clinical, Histologic, and Immunohistochemical Review of 129 Cases

Ramos‐Vara, José A.; Beissenherz, Marilyn E.; Miller, Margaret A.; Johnson, Gayle C.; Pace, Lanny W.; Fard, Ali; Kottler, Stephanie J.

doi:10.1354/vp.37-6-597

Cited by 274 publications

(476 citation statements)

References 39 publications

Supporting

Mentioning

355

Contrasting

Unclassified

Order By: Relevance

“…11 In a previous study, antibody A103 only stained the ductular epithelium in the canine pancreas. 17 In the present study, antibody A103 reacted with adrenocortical cells, granulosa-theca cells of the ovary, and Leydig and Sertoli cells of the testis. Reactivity to A103 antibody was also present in the cytoplasm of interstitial cells of the ovary, which has not been reported in human tissues.…”

Section: Discussionsupporting

confidence: 56%

“…4,6,8 More than 90% of canine oral melanomas are also positive for Melan A. 17 In recent studies, a monoclonal antibody (clone A103) to Melan A was used to detect human steroid-producing cells (and their corresponding tumors), including adrenal cortical cells, granulosa cells of the ovary, and Leydig cells of the testicle. 5,11,18,20 The apparent absence of Melan A in these tissues suggests that reactivity is the result of cross-reaction with a similar protein.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immunoreactivity of A103, An Antibody to Melan A, in Canine Steroid-Producing Tissues and their Tumors

et al. 2001

View full text Add to dashboard Cite

Abstract. The monoclonal antibody A103 to the melanocytic differentiation antigen Melan A stains human steroid-producing cells and their tumors. A total of 200 formalin-fixed, paraffin-embedded canine normal tissues and hyperplastic and neoplastic lesions of the adrenal gland, testis, and ovary were immunohistochemically tested for Melan A with antibody A103. Leydig cell tumors (23/23, 100%), Sertoli cell tumors (14/15, 93%), and adrenocortical adenomas (12/13, 92%) were consistently positive. Adrenocortical carcinomas (23/35, 65%) and granulosa cell tumors (10/17, 59%) were less frequently positive. All pheochromocytomas, seminomas, and dysgerminomas were negative. The pattern of staining was cytoplasmic, but nuclear staining was also frequently seen in normal Leydig cells and their tumors. As in human tumors, immunohistochemistry for Melan A stains many canine steroid-producing tumors and can be used to distinguish these tumors from those of nonstereidogenic cells.Melan A belongs to a group of melanocytic differentiation antigens, including tyrosinase, gp 100, human melanosome-associated antigen, and microphthalmia transcription factor. 1,3,10,13,19 Melan A is an antigen that is recognized by autologous cytotoxic T cells. 8,12 This protein is coded by the MART 1 gene 9,12 and is a highly specific immunohistochemical marker for human melanomas. 4,6,8 More than 90% of canine oral melanomas are also positive for Melan A. 17 In recent studies, a monoclonal antibody (clone A103) to Melan A was used to detect human steroid-producing cells (and their corresponding tumors), including adrenal cortical cells, granulosa cells of the ovary, and Leydig cells of the testicle. 5,11,18,20 The apparent absence of Melan A in these tissues suggests that reactivity is the result of cross-reaction with a similar protein. 4 The diagnosis of canine endocrine tumors can be challenging, especially when it is necessary to distinguish between cortical and medullary adrenal tumors and their metastases. In the present report, the immunohistochemical detection of Melan A in formalinfixed, paraffin-embedded tissues of normal and neoplastic tissues from the adrenal gland, ovary, and testis of dogs is described. Health Diagnostic Laboratory databases were searched for biopsies and necropsies containing adrenal gland, ovarian, or testicular tumors. A total of 200 normal, hyperplastic, or neoplastic tissues, including testicular tumors (Leydig cell tumor, Sertoli cell tumor, and seminoma), ovarian tumors (granulosa-theca, luteoma, dysgerminoma, and carcinoma), and adrenal lesions (adrenal cortical hyperplasia, adrenocortical adenoma, adrenocortical carcinoma, and pheochromocytoma) corresponding to 182 canine accessions were selected for this study. Diagnoses were initially made by the case coordinator; every case was reviewed by another pathologist (JAR) using reported classification criteria. 2,14,15 If discrepancies in the diagnosis based on hematoxylin and eosin-stained sections were found, a consensus among 3 pathologists was reached. Tissu...

show abstract

Section: Discussionsupporting

confidence: 56%

mentioning

confidence: 99%

Immunoreactivity of A103, An Antibody to Melan A, in Canine Steroid-Producing Tissues and their Tumors

et al. 2001

View full text Add to dashboard Cite

show abstract

“…This highly aggressive canine tumor is too invasive to be cured only by surgical resection and is frequently resistant to current therapies. 1,2 This has prompted investigations to define new treatment strategies. Intratumor suicide non-viral gene therapy with thymidine kinase from the herpes simplex virus (HSVtk), in combination with the pro-drug ganciclovir (GCV), is one of the emerging strategies against this malignant disease.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Although this property of tumors was focused for over 20 years on multidrug resistance (MDR), other kind of resistance called multicellular resistance (MCR) produced by a solid tissue environment is the major obstacle to many cancer therapies. 7,8 This intrinsic in vivo resistance might not be observed when cells are cultured as monolayers.…”

Section: Introductionmentioning

confidence: 99%

Suicide gene therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro

et al. 2009

View full text Add to dashboard Cite

To validate the use of multicellular spheroids to predict the efficacy of herpes simplex thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene therapy in the respective in vivo tumors, we established and characterized 15 melanomaderived cell lines from surgically excised melanoma tumors. Three HSVtk-lipofected cell lines were not sensitive to GCV in any culture configuration, other five displayed similar sensitivity as monolayers or spheroids, and only one resulted more sensitive when grown as spheroids. Other six cell lines manifested a relative multicellular resistance (MCR) phenotype growing as spheroids, compared with the same cells growing as monolayers. The reverse correlation between the MCR and the monolayers survival to HSVtk/GCV suggests that one of the main causes of MCR would be the rapid cell repopulation after suicide gene treatment. The high correlation of MCR with the spheroids radial growth and with the mitotic index of the respective originary tumors supported this re-growth involvement. A remarkable finding was the high correlation in HSVtk/GCV sensitivity between in vivo tumor and the corresponding derived cell lines growing as spheroids (R 2 ¼ 0.85). This strongly encourages the implementation of spheroids as highly realistic experimental model for optimizing and predicting the in vivo response of the respective tumors to therapeutic strategies.

show abstract

“…Like human melanoma, the prognosis for canine malignant melanoma correlates directly with tumor stage. 2,3 At the time of diagnosis, the disease is habitually metastatic and has an extremely poor prognosis. All the efforts of conventional treatments including extended resection, radiation, chemotherapy and conventional biological response modifiers such as Bacille Calmette-Gue´rin or Corynebacterium parvum extracts, have little influence on patients, survival.…”

Section: Introductionmentioning

confidence: 99%

Suicide gene and cytokines combined nonviral gene therapy for spontaneous canine melanoma

et al. 2008

View full text Add to dashboard Cite

Canine spontaneous melanoma is a highly aggressive tumor resistant to current therapies. We evaluated the safety, efficacy and antitumor effects of direct intratumor injections of lipoplexes encoding herpes simplex thymidine kinase coadministrated with ganciclovir, and irradiated transgenic xenogeneic cells secreting 20-30 mg day À1 of human granulocyte-macrophage colonystimulating factor and interleukin-2. Toxicity was minimal or absent in all patients. This combined treatment (CT) induced tumor regression and a pronounced immune cell infiltration. The objective responses (47%: 21/45) averaged 80% of tumor mass loss. Local CT also induced systemic antitumor response evidenced by complete remission of one pulmonary metastasis and by the significantly higher percentage of metastasis-free patients (76: 34/45)) until the study ending compared to untreated (UC: 29%, 5/17), surgery-treated (CX: 48%, 11/23) or suicide gene-treated controls (SG: 56%, 9/16) (Fisher's exact test). CT significantly improved median survival time: 160 (57-509) days compared to UC (69 (10-169)), or ). CT also increased (Po0.00001, Kaplan-Meier analysis) metastasis-free survival: 4509 (57-509) days with respect to UC: 41 (10-169), CX: 133 (43-216) and SG: 4159 (41-159). Therefore, CT controlled tumor growth by delaying or preventing distant metastasis, thereby significantly extending survival and recovering the quality of life.

show abstract

Retrospective Study of 338 Canine Oral Melanomas with Clinical, Histologic, and Immunohistochemical Review of 129 Cases

Cited by 274 publications

References 39 publications

Immunoreactivity of A103, An Antibody to Melan A, in Canine Steroid-Producing Tissues and their Tumors

Immunoreactivity of A103, An Antibody to Melan A, in Canine Steroid-Producing Tissues and their Tumors

Suicide gene therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro

Suicide gene and cytokines combined nonviral gene therapy for spontaneous canine melanoma

Contact Info

Product

Resources

About