scholarly journals Quantitative Expression of TYR, CD34, and CALD1 Discriminates Between Canine Oral Malignant Melanomas and Soft Tissue Sarcomas

2021 ◽  
Vol 8 ◽  
Author(s):  
Mayra F. Tsoi ◽  
Tuddow Thaiwong ◽  
Rebecca C. Smedley ◽  
Erica Noland ◽  
Matti Kiupel

Canine oral malignant melanomas (OMMs) exhibit a variety of morphologic phenotypes, including a spindloid variant. The microscopic diagnosis of spindloid OMMs is based on junctional activity and/or the presence of melanin pigment. In the absence of these features, spindloid OMMs are difficult to differentiate from soft tissue sarcomas (STS). An antibody cocktail (MDX) that includes Melan-A, PNL2, and tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) is the current gold standard for identifying amelanotic OMMs by immunohistochemistry (IHC). However, MDX is less sensitive for diagnosing spindloid amelanotic OMMs. This raises concern for biopsy specimens that lack overlying epithelium, making it potentially difficult to differentiate OMM from STS by IHC. The goal of this study was to identify additional markers to help differentiate between STS and OMMs that lack pigment and junctional activity. SOX-10 has recently been proposed as a sensitive marker for melanocytes in humans but has not been validated in dogs. Similarly, RNA expression for various genes has been analyzed in humans, but not in the context of diagnosing canine melanocytic neoplasms. For this retrospective study, formalin-fixed, paraffin-embedded tissues from 20 OMMs, 20 STS, and 20 oral spindle cell tumors (OSCTs) that lacked junctional activity and pigmentation were selected. IHC for MDX, SOX-10, and laminin, in parallel with RT-qPCR of TYR, SOX10, CALD1, CD34, DES, and LAMA1, was performed in all cases. TYR, CD34, and CALD1 were the most discriminatory genes in differentiating between OMM and STS, all having 100% specificity and 65, 95, and 60% sensitivity, respectively. While all 20 OMMs were immunohistochemically labeled for SOX-10, two STS were also labeled (100% sensitivity and 90% specificity). MDX IHC labeled all 20 OMMs and no STS. Surprisingly, none of the 20 OSCTs expressed TYR RNA above the cutoff, and 14/20 OSCTs expressed CALD1 or CD34 RNA above the cutoff, thereby confirming them as STS. Four OSCT were suspect STS, and no OSCTs were confirmed as OMMs based on IHC and RNA expression patterns. In conclusion, the RNA levels of TYR, CD34, and CALD1 should be evaluated in suspected amelanotic OMMs that are negative for MDX to accurately differentiate between OMM and STS.

2021 ◽  
pp. 104063872110222
Author(s):  
Samantha M. Norris ◽  
Paula A. Schaffer ◽  
Noah B. Bander

A 15-y-old castrated male Maine Coon cat was evaluated for an ulcerated soft tissue mass on the right hindlimb that had been observed for 4 mo and had grown rapidly. A 3 × 3 cm soft, raised, amorphous, and ulcerated subcutaneous mass was observed on the lateral right metatarsus. In-house cytology via fine-needle aspiration was nondiagnostic. Incisional biopsy of the mass and further staging was declined, and amputation was elected. The amputated limb was submitted for histopathology, which revealed severe chronic nodular granulomatous dermatitis and multifocal granulomatous popliteal lymphadenitis with large numbers of intralesional fungal hyphae. Fungal PCR and sequencing on formalin-fixed, paraffin-embedded tissue identified Chalastospora gossypii. No adjunctive therapy was elected at the time. The patient has done well clinically 1 y post-operatively. C. gossypii is a rare microfungus found worldwide and is considered a minor pathogen of several plants. To our knowledge, infection by this fungus has not been reported previously in veterinary species. Features in our case are comparable to other mycotic infections. Nodular granulomatous mycotic dermatitis and cellulitis, although uncommon, should be a differential for soft tissue masses in veterinary species; C. gossypii is a novel isolate.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4755-4755
Author(s):  
Stefan Wirths ◽  
Hans-Joerg Buehring ◽  
Lothar Kanz ◽  
Joerg T Hartmann ◽  
Hans-Georg Kopp

Abstract Malignant tumors are hypothesized to harbor small populations of self-renewing cancer stem cells. Targeting these cells may be the decisive step to overcome treatment resistance and achieve tumor eradication in cancer patients. Advanced soft tissue sarcomas (STS) are rare tumors with a dismal prognosis and a small number of systemic treatment options. STS may originate from mesenchymal stem cells (MSC); the latter have mainly been isolated from adult bone marrow (BM) as non-hematopoietic, self-renewing cells whose in vitro progeny comprises osteoblasts, chondroblasts, myocytes, and adipocytes. While in vitro expression profiles of MSC have been investigated extensively, the in vivo counterparts of MSC are still hypothetical. To target rare human cell BM populations including MSC, an exclusive antibody panel was developed. The target antigens include platelet-derived growth factor receptor-β (CD140b), HER-2/erbB2 (CD340), the recently described W8B2 antigen as well as several surface antigens identified by novel antibodies. To define the expression pattern of MSC-markers in STS, three STS cell lines were tested for expression of these antigens. In addition, snap-frozen primary STS sections were analyzed by immunohistochemistry using the same antibody panel. All cell lines revealed expression of selected markers including CD340, W8B2, and CD140b. Several MSC markers were restricted to a subpopulation of cells. In addition, leiomyosarcoma cells displayed a different expression pattern as compared to liposarcoma and Ewing’s sarcoma cells. Results of immunohistochemistry analysis of primary leiomyosarcoma tumor samples correlated strongly with expression patterns established by FACS analysis. However, important cytoarchitectural features regarding selected markers were revealed by immunohistochemistry: while primary leiomyosarcomas displayed uniform expression of W7C6, HEK3D6, CD10, and CD318, other markers such as CD34, W5C5, and 57D2 were expressed by tumor endothelia only. Moreover, a population of perivascular tumor cells was found to express the MSC-markers W4A5, W8B2, CD140b, W3D5, and W5C4. Novel MSC-markers are expressed by subpopulations in STS cell lines as well as in primary sarcoma tissue. Further studies on the functional significance of these phenotypical studies are underway and may help to identify novel specific targets recognizing the self-renewing STS-compartment.


2014 ◽  
Vol 210 (12) ◽  
pp. 804-811 ◽  
Author(s):  
Heike Horn ◽  
Jan Allmanritter ◽  
Claudio Doglioni ◽  
Alexander Marx ◽  
Justus Müller ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4877
Author(s):  
Luc M. Berclaz ◽  
Annelore Altendorf-Hofmann ◽  
Hans Roland Dürr ◽  
Alexander Klein ◽  
Martin K. Angele ◽  
...  

Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A (“Top survivors”) significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the “Top survivor” biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.


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