Figure 6 - uploaded by Costantino Ricci
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Graphical representation of PRAME expression (% of positive cells and intensity) in MBML-H&N and MM-H&N. Each case corresponds to 2 bars, one for the % of PRAME-positive cells (green: MBML-H&N, pink: mucosal lentiginous MM-H&N, blue: nodular MM-H&N) and one for the intensity (orange bars). Fifteen cases showed 0% of PRAME-positive cells (13 MBML-H&N and 2 mucosal lentiginous MM-H&N; see the Results section and Fig. 5 for more explanations). Notably, the majority of MM-H&N below the cutoff of 60% of PRAME-positive cells (red dotted line) are mucosal lentiginous (only 1 case was nodular); all MBMLH&N show % of PRAME-positive cells below this threshold.
Source publication
PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal...
Citations
... 10 Recently, PRAME (PReferentially expressed Antigen in MElanoma) has been introduced as a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. 11 According to Ricci et al., 11 high PRAME expression (⩾60%) in mucosal melanocytic tumors was highly suggestive of melanoma. ...
... 10 Recently, PRAME (PReferentially expressed Antigen in MElanoma) has been introduced as a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. 11 According to Ricci et al., 11 high PRAME expression (⩾60%) in mucosal melanocytic tumors was highly suggestive of melanoma. ...
Primary non-cutaneous melanoma is a rare type of melanoma that occurs mostly on mucosal surfaces. The head and neck region is the most common site for these melanomas. The following cases described herein include patients diagnosed with primary non-cutaneous melanomas. The locations included the parotid gland (one case), the submandibular gland (one case), and the nasal cavity and paranasal sinuses (three cases). Among these patients, one patient developed lymph node metastasis and one patient had distant metastasis. Treatment included endoscopic surgery (one case), endoscopic surgery with adjuvant radiotherapy (one case), open surgery (one case), and palliative chemotherapy (one case). One patient refused to receive treatment. After treatment, one patient had local recurrence. A local and distant recurrence was noted in one case. This report aims to describe clinical features, treatment options, and prognosis of primary non-cutaneous melanomas of the head and neck.
... A study by Ricci et al. found that most benign melanocytic lesions of the mucosa of the head and neck do not show positive immunostaining for PRAME. However, a minority of cases show rare positive cells scattered in the lesion without significant changes in the expression intensity or location [38]. On the other hand, a study by Toyama et al. reported that most mucosal melanomas express PRAME and a high PRAME expression correlates with a poor prognosis. ...
... In conclusion, PRAME is more commonly expressed in malignant mucosal melanocytic lesions and its increased expression is associated with a poor prognosis. This factor appears to be a prognostic indicator independent of other factors, such as NRAS mutations, and its expression does not appear to correlate with the specific location of a malignant mucosal lesion [34,38,39]. PRAME expression is highly sensitive and specific in the context of acral melanomas and is a more predictive diagnostic tool than p16 immunohistochemistry. Acral dysplastic nevi and acral Spitz nevi may show significant architectural and cellular atypia (a large nuclear size, irregularly shaped nuclei, hyperchromatic nuclei, or prominent nucleoli), which makes them difficult to distinguish from acral melanoma. ...
... Benign mucosal melanocytic lesions NO PRAME expression [35,39] Mucosal melanoma ↑ PRAME expression [35,38,39] Lymph nodes nevi(nodal nevi) NO PRAME expression [34] Lymph nodes metastases ↑ PRAME expression [34] ...
Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.
... Recently, PRAME expression has received much attention in some types of malignant tumor as a useful diagnostic marker due to its nature of being a cancer/testis antigen [13]. Notably, malignant melanoma and its mimics represents the most intensively investigated area of PRAME expression [14][15][16][17][18][19][20][21][22][23][24]. Numerous articles have examined the expression profiles of PRAME in malignant melanoma and have demonstrated its diagnostic utility. ...
... Numerous articles have examined the expression profiles of PRAME in malignant melanoma and have demonstrated its diagnostic utility. Specifically, most cases of malignant melanoma exhibited positive immunoreactivity to PRAME; in contrast, most benign melanocytic nevi did not [14][15][16][17][18][19][20][21][22][23][24]. Moreover, PRAME expression has also been reported in various types of malignant tumor, other than malignant melanoma, including myxoid liposarcoma, synovial sarcoma, neuroblastoma, renal cell carcinoma, non-small-cell lung cancer, and thymic cancer [8,13,14,[25][26][27][28][29][30]. ...
... The expression of PRAME has been reported in various types of malignant tumor [8,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Notably, the present study is the first study to clearly demonstrate that PRAME was expressed in 43.4% of CIS of the urinary tract. ...
Carcinoma in situ (CIS) of the urinary tract comprises 1–3% of all urothelial malignancies and is often a precursor to muscle-invasive urothelial carcinoma (UC). This study aimed to examine the expression profiles of preferentially expressed antigen in melanoma (PRAME), a cancer/testis antigen, and assess its diagnostic and therapeutic applications in CIS, given that its expression in UC has been minimally studied and has not yet been analyzed in CIS. We selected consecutive patients with CIS who underwent biopsy and/or transurethral tumor resection at the Osaka Medical and Pharmaceutical University Hospital. Immunohistochemical staining for PRAME and p53 was performed. Overall, 53 patients with CIS (6 females and 47 males) were included. Notably, PRAME expression was observed in 23 of the 53 patients (43.4%), whereas it was absent in the non-neoplastic urothelial epithelium. Furthermore, no correlation was found between PRAME expression and aberrant p53 expression. Therefore, PRAME expression may serve as a useful marker for CIS of the urinary tract. Furthermore, PRAME may be a candidate for the novel therapeutic target for standard treatment-refractory CIS patients.
... In a recent study, 98.1% of all nevi tested lacked PRAME expression, while six nevi showed a focal positivity [7]. Also, in another study, Ricci and his colleagues found that head and neck mucosal melanomas are characterized by PRAME expression [8]. In addition, they observed that high PRAME expression was associated with nodular histotype and interestingly, female gender. ...
Background
Penile melanoma (PM) is a rare tumor, accounting for less than 2% of all penile cancers. PM can occur on the surface of the glans, foreskin, and opening of the urethra. Furthermore, PM primarily affects older individuals and is not associated with sun exposure. Currently, there is no specific staging system for genitourinary tract melanomas, so these tumors are typically staged using the criteria for cutaneous melanoma. Limited data in the literature suggests that PM generally has a poor clinical prognosis.
Case presentation
Here, we describe two cases of PM. The first case affected a 62-year-old male who presented with hematuria and a painful tumor in the distal urethra, leading to a suspicion of penile cancer. The second case involved a 68-year-old male who noticed a rapidly evolving dark spot on his foreskin. Histological analysis confirmed the presence of melanoma in both patients. The tumors showed a diffuse and strong PRAME-positivity and lacked BRAF mutation in both cases. Additionally, the second tumor harbored an activating CKIT mutation. An enhanced PD-L1 expression was observed in both tumors.
Conclusions
We presented two rare forms of mucosal melanoma and highlighted the entities in the differential diagnosis. Based on our experience PRAME is a helpful marker for making the diagnosis of PM, and PD-L1 can predict the success of the immunotherapy. We also emphasize the need for an organ-specific staging system for PMs.
... A recent study in mucosal melanoma of the head and neck region showed that PRAME expression could be used for the accurate diagnosis of head-and-neck melanocytic tumors. Furthermore, high expression (≥60%) of PRAME was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex [107]. ...
Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis, and is overexpressed in various cancers. PRAME family proteins are leucine-rich repeat proteins that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcomes in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.
... A recent study in mucosal melanoma of the head and neck region showed that PRAME expression could be used for the accurate diagnosis of head and neck melanocytic tumors. Furthermore, high expression (≥60%) of PRAME was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex [106]. ...
Preferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis and is overexpressed in various cancers. PRAME family proteins are leucine rich repeat proteins, that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcome in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.
