Dermatopathological indicators of poor melanoma prognosis are significantly inversely correlated with the expression of NM23 protein in primary cutaneous melanoma
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Abstract:
Some dermatopathological parameters are recognized as dominant indicators of high metastatic potential in melanoma, especially Breslow thickness, ulceration, Clark's level of invasion and mitotic rate. Because NM23 protein is the product of a melanoma metastasis suppressor gene, the aim of this study was to compare such dermatopathological indicators of melanoma prognosis with NM23 protein expression in primary cutaneous melanoma.The immunohistochemical NM23 expression was semiquantitatively assessed in 30 primary cutaneous melanomas. Ten dermatopathological parameters were evaluated and compared with NM23 expression.A significant inverse correlation was found for NM23 expression in comparison with Breslow thickness (p < 0.01), ulceration (p < 0.05), Clark's level (p < 0.01), mitotic rate (p < 0.05), and vertical growth phase (p < 0.05). By contrast, no significant correlation was found for NM23 expression in comparison with cell morphology, presence of adjacent nevus, pigmentation, tumor-infiltrating lymphocytes, and regression was impossible to evaluate.The expression of NM23 protein in primary cutaneous melanoma is significantly inversely correlated with dermatopathological parameters currently recognized as powerful indicators of melanoma prognosis. NM23 may be therefore considered in the dermatopathological evaluation of primary cutaneous melanoma.Keywords:
Breslow Thickness
Nodular melanoma
Patients who are already diagnosed with cutaneous melanoma are at increased risk of developing another primary melanoma. The occurrence of multiple primary melanoma is a rare phenomenon, varying in frequency, with an estimated incidence ranging from 0.2% to 8.6%. The authors are presenting data on the patients with multiple primary melanoma from the Croatian Referral Melanoma Centre. The clinical, histological and epidemiological characteristics of 36 (3.6%) patients, identified from 991 patients with histologically confirmed melanoma, are analyzed in this study. Twenty-eight of the patients (78%) had two primary melanomas, six had three melanomas (16.7%) and two (5,6%) had four melanomas. Diagnosis was established synchronously in 11 patients (30%) and, in the rest of the patients, time interval between the diagnosis of the first and second melanoma varied from 1 month to the longest interval of 16 years. However, the majority of subsequent melanomas were removed within 2 years of the initial operation. The mean Breslow's thickness of the first melanoma was significantly higher than the mean Breslow's thickness of the second primary melanoma. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Therefore, we emphasize the importance of regular follow-up as well as the education in regular self--skin examinations in melanoma patients in order to detect subsequent primary melanomas in the early phase.
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Breslow Thickness
Surgical oncology
Medical record
Presentation (obstetrics)
Nodular melanoma
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Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified junctional adhesion molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C(-/-) mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis.
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Two hundred thirty-nine cases of primary cutaneous malignant melanoma were submitted to a multifactorial analysis of histological criteria. Three of those criteria, namely, Breslow's thicknesses, ulceration, and mitotic activity, were found to be significant for prognosis.
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Introduction
In Sweden, the incidence of cutaneous malignant melanoma rises yearly with 5.5% for men and 5.2% for women and has now reached world standard rates of 17.6 for men and 18.8 for women per 100,000 population. Over the past decades, the incidence of melanoma has been higher in Western Sweden than the national average. Previous international studies have shown that melanoma patients have an elevated risk of developing a new separate primary melanoma. This study aimed at describing multiple primary melanomas (MPMs) in Western Sweden with focus on the number of tumours detected, tumour characteristics and the time to diagnosis of a subsequent melanoma.
Methods
Data was extracted retrospectively from the Swedish Melanoma Registry and provided information on all invasive and in situ melanoma cases in Western Sweden (1.6 million inhabitants) from 1990 to 2013.
Results
Within the studied period, 12,152 patients developed 13,291 melanomas. 11,254 of the patients developed only a single primary melanoma. In total, 898 patients (7.4% of all melanoma patients) developed 2,037 MPMs. Preliminary results show that the median Breslow thickness for all invasive melanomas was below 1 mm. The median Breslow thickness for the MPMs was slightly thinner for the second and third invasive melanoma as compared to the first invasive melanoma. Further, there was a higher percentage of in situ tumours among the subsequent melanomas. The median time to diagnosis of a subsequent melanoma was approximately 3 years.
Discussion
Subsequent primary melanomas in Western Sweden are most commonly diagnosed with a somewhat thinner Breslow thickness than the first primary melanoma. The comparatively high percentage of melanoma survivors developing MPMs and the short median time to diagnosis of a subsequent melanoma stresses the importance of follow-up for melanoma patients, particularly during the first years.
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Abstract Background Melanomas can arise from naevi or appear de novo . The frequency or the effect of their origin on prognosis is still debated. Mitotic rate (MR) and ulceration of melanomas have been proposed as further new prognostic indexes. Aim To determine the different prognostic factors in melanomas de novo and melanomas from pre‐existing naevi and whether these two melanoma groups have different MR or presence of ulceration. Methods All patients with confirmed primary melanomas observed in our clinic from 1996 to July 2013 were included. The distinction between the two groups of melanomas was histologically based. We compared Breslow's thickness, the number of mitosis/mm 2 and the presence of ulceration between the naevus‐associated melanoma and de novo melanoma group. Results Of the 873 melanomas, 626 (71.8%) have a de novo melanoma, 247 (28.2%) a naevus‐associated melanoma. Breslow's thickness was not significantly different in the two groups (0.77 ± 1.47 mm vs. 0.59 ± 1.35 mm). The number of patients with presence of ulceration and MR ≥1 mitosis/mm 2 was not significantly different in the two groups (19.6% vs. 16.3%). In thicker melanomas (Breslow's thickness ≥ 1 mm), the number of patients with ≥6 mitosis/mm 2 was significantly higher (26.6% vs. 7.9%; P < 0.05) in the de novo melanoma group. Conclusions When mitosis ≥ 1 mm/mm 2 , the results obtained do not show a better or worse prognosis based on Breslow's thickness, ulceration and MR in melanomas associated with naevus vs. melanomas de novo . When ≥6 mitosis/mm 2 are considered, the number of patients in the de novo melanoma group with thick melanoma is highly more represented. The debate about the cut‐off value of mitosis ≥1 mm 2 is open.
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This chapter presents a comprehensive summary of the basic criteria that are critical to the histologic diagnosis of melanoma. It focuses on the clinical features of the prototypic subgroups of melanoma such as lentiginous melanoma. After a consideration of the clinical features, the histology of the radial growth phase as it relates to specific subtypes of melanoma is addressed followed by a discussion on the recognition of the vertical growth phase. Five-year survival rates according to measured Breslow thickness are given in the chapter for patients with stage I lesions, where the tumor is confined to the primary site of the melanoma without regional lymph node involvement or distant metastatic disease. Unusual forms of melanoma are discussed at the end of the chapter.
Acral lentiginous melanoma
Nodular melanoma
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Histology
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Some dermatopathological parameters are recognized as dominant indicators of high metastatic potential in melanoma, especially Breslow thickness, ulceration, Clark's level of invasion and mitotic rate. Because NM23 protein is the product of a melanoma metastasis suppressor gene, the aim of this study was to compare such dermatopathological indicators of melanoma prognosis with NM23 protein expression in primary cutaneous melanoma.The immunohistochemical NM23 expression was semiquantitatively assessed in 30 primary cutaneous melanomas. Ten dermatopathological parameters were evaluated and compared with NM23 expression.A significant inverse correlation was found for NM23 expression in comparison with Breslow thickness (p < 0.01), ulceration (p < 0.05), Clark's level (p < 0.01), mitotic rate (p < 0.05), and vertical growth phase (p < 0.05). By contrast, no significant correlation was found for NM23 expression in comparison with cell morphology, presence of adjacent nevus, pigmentation, tumor-infiltrating lymphocytes, and regression was impossible to evaluate.The expression of NM23 protein in primary cutaneous melanoma is significantly inversely correlated with dermatopathological parameters currently recognized as powerful indicators of melanoma prognosis. NM23 may be therefore considered in the dermatopathological evaluation of primary cutaneous melanoma.
Breslow Thickness
Nodular melanoma
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Background
Incidence and mortality of melanoma in the United States have risen steeply. Part of this mortality increase may be related to late detection of biologically aggressive nodular melanomas. We determined trends in distribution of thin and thick melanoma, with emphasis on the histopathologic subtype nodular melanoma.Methods
Surveillance, Epidemiology, and End Results melanoma incidence data for whites were obtained for 1988 through 1999 and stratified according to histologic subtype: lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, other, and not otherwise specified (NOS); thickness: 0-0.99 mm, 1.00 mm-1.99 mm, and ≥2.0 mm; patient age (0-49, 50+); gender; and year (1988-1991, 1992-1995, 1996-1999). Comparison of tumor thickness between strata was defined by year of diagnosis, sex, age, and histologic subtype.Results
The number of new melanoma cases in a 3-year period increased 60% from 1988-1991 (n = 9132) to 1996-1999 (n = 14 575). The proportion of thick melanomas (≥2 mm) remained relatively stable during the 12 study years. Nodular melanoma comprised 9% of all recorded cases but 34% of melanomas 2 mm or larger, including melanoma not otherwise specified (NOS), and nearly 50% of all melanomas 2 mm or larger when NOS cases were excluded. In contrast, superficial spreading melanoma was almost uniformly diagnosed as an early tumor, mostly (77%) presenting as thin melanoma (<1 mm) and with only 7% presenting as thick melanoma (≥2 mm).Conclusions
A substantial number of thick melanomas in the United States are of the nodular subtype, and median thickness of nodular melanoma has not changed during the 12 years of study. New strategies are needed to decrease the incidence of thick melanoma in the United States.Nodular melanoma
Superficial spreading melanoma
Lentigo maligna melanoma
Lentigo maligna
Lentigo
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The incidence of cutaneous melanoma has increased significantly worldwide over the last several decades. The aim of this study is to determine clinical and morphology characteristics of primary melanoma, since some of them are important prognostic factors. This retrospective study included 172 patients. The data were collected by the Consulting team for malignant skin tumors in the Banja Luka Clinical Centre from 2009 to 2011. We did not use dermoscopy as a diagnostic tool in our investigation. We determined that melanoma occurs equally commonly in both sexes, in women in the sixth decade and the seventh in men. The most common sub-type was nodular melanoma (59.5%, P<0.05), followed by superficial spreading (27.8%) and acral lentiginous melanoma (11.4%). The most common localization was on the back in men (34.3%) and on the legs in women (P<0.05). More than half of our patients (55.8%) had melanoma thickness from 1.0 to 4.0 mm, and 38% had a melanoma thicker than 4.0 mm. The average Breslow thickness is 4.6 mm. More women than men had melanoma thicker than 4 mm (P<0.05). Spread of the primary tumor localization was found in 31.4% of patients, more frequently in men than in women (P<0.05). In most cases it was abstraction of lymph nodes (P<0.05). The average thickness of the melanoma in our patients is much higher than the average in the world and the countries of Europe. The results of this study indicate a need for better unique regional registry in this part of Bosnia and Herzegovina and improvement of preventive measures in the early diagnosis of melanoma.
Acral lentiginous melanoma
Nodular melanoma
Breslow Thickness
Superficial spreading melanoma
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