nm23蛋白在恶性黑素瘤中的表达

目的：探讨nm23蛋白在恶性黑素瘤（恶黑）中的表达及和临床病理参数、预后的关系。方法：采用免疫组化方法（Envision法）对30例恶黑中nm23蛋白表达进行了检测，并进行了临床病理相关性研究。结果：发现nm23的表达与恶黑淋巴结转移、有复发、脏器转移呈负相关（P＜0．05），与生存期呈正相关（P＜0．001）。结论：nm23蛋白表达对恶黑的转移、复发具有负调控作用，nm23蛋白低表达恶黑具有高转移潜能，而高表达者预后相对好，淋巴结转移率、复发率、脏器转移率均低，生存期长。     

恶性黑素瘤p53、C-erbB2蛋白表达的临床病理意义探讨

为了探讨p53及C－erbB2在恶性黑素瘤（恶黑）中的表达及意义，采用免疫组化方法对28例恶黑皮损中p53及C－erbB2蛋白表达进行了检测，并进行临床病理相关性研究。结果发现，p53的表达与黑素复发，脏器转移呈正相关（P＜0．05），与生存期呈负相关（P＜0．05），与年龄，肿瘤大小，淋巴结转移，病理学分级无统计学意义，C-erbB2的表达与恶黑淋巴结转移，复发，脏器转移呈正相关（P＜0．05），与生存期呈负相关（P＜0．05），与年龄，肿瘤大小，病理学分级无统计学意义，p53，C－erbB2，在恶黑中的共同表达未发现相关关系，p53,C-erbB2在恶黑中可作为一种生物学恶性程度高，预后不良的指标。     

Rising levels of serum S100 protein precede other evidence of disease progression in patients with malignant melanoma

BACKGROUND: Several serum markers may be useful in the detection of metastatic melanoma, but none is in routine clinical use. OBJECTIVE: To assess the validity of S100 protein as a serum marker of melanoma progression. METHODS: Serum S100 protein levels were measured in 496 serum samples from 214 melanoma patients, using the Sangtec luminescence immunoassay. There were 75 patients with stage 1 melanoma, 66 initially with stage 2 melanoma, 49 initially with stage 3 melanoma and 24 with stage 4 melanoma. RESULTS: Serum S100 protein levels were < 0.2 microg L-1 in 71 of 75 (95%) stage 1 patients. One patient who had a normal level developed local recurrence. Fifty-eight of 66 (88%) stage 2 patients also had normal serum S100 protein levels. One with elevated levels progressed to stage 3 melanoma and five with elevated levels progressed to stage 4 disease. The remaining two with elevated serum S100 protein remained well. Thirty-five of 49 (71%) stage 3 patients had normal levels and, of these, two have progressed to stage 4 disease. Three patients with stage 3 disease had an elevated serum S100 protein level on one occasion but remained well. Eleven of 13 patients who developed stage 4 melanoma during the study had rising levels of serum S100 protein > 0.2 microg L-1 5-23 weeks before detection of melanoma progression by conventional means. Twenty-two of 24 patients with stage 4 disease throughout the study had consistently elevated serum S100 protein levels, and the two patients with normal levels were clinically disease free after surgery and chemotherapy. None of 14 control subjects with atypical naevi had elevated S100 protein levels, and only one of 11 healthy normal controls had an elevated level. CONCLUSIONS: Thus, rising levels of serum S100 protein are a specific and sensitive clinically relevant marker of tumour progression in melanoma patients, which precedes other evidence of melanoma recurrence.     

Progress of multiple cutaneous and subcutaneous melanoma metastases of the face during imiquimod treatment

A 68‐year‐old man developed a local recurrence with multiple cutaneous and subcutaneous nodules three months after excision of a primary malignant melanoma of the temple. Despite extensive surgery and adjuvant irradiation, another local recurrence occurred. Following further local progression during dacarbazine chemotherapy, topical treatment with imiquimod was begun and the chemotherapy was changed to fotemustine. During this treatment further local progression occurred and two months later regional lymph node and distant metastasis were detected. The patient died from his tumor disease eighteen months after the first diagnosis of malignant melanoma.     

Chronic granulomatous dermatitis induced by talimogene laherparepvec therapy of melanoma metastases

Talimogene laherparepvec (TVEC) is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing granulocyte macrophage‐colony stimulating factor (GM‐CSF) and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB‐IV M1a melanoma. However, clinical response assessment can be problematic due to immune‐related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients. Over 5 months, TVEC injections were administrated in a median of 20 tumors per patient for 9 median doses prior to biopsy of persistent, indurated nodules. Granulomatous dermatitis with melanophages and melanin pigment incontinence was observed in all samples without evidence of melanoma cells in 4 patients. The fifth patient was rendered melanoma‐free by resection of the 1 nodule out of 4 with persistent tumor. Repetitive administration of TVEC or other oncolytic viral immunotherapies mimicking unresolved infection can produce granulomatous inflammation confounding assessment of the degree of tumor response and need for additional TVEC therapy. Tumor biopsies are encouraged after 4 to 6 months of TVEC administration to differentiate melanoma from granulomatous inflammation. Patients with confirmed granulomatous dermatitis replace continued with remained in remission after treatment discontinuation. Inflammatory nodules typically regress spontaneously.     

Pagetoid malignant melanoma and lentigo maligna melanoma of toe

Summary Two cases of malignant melanoma on the toe of middle-aged women were examined chiefly by the fluorescence method of Falck and Hillarp. In one of the patients, histopathology of the pigmented tumor on the left middle toe was a Pagetoid (superficial spreading) melanoma in situ, and the subungual granulomatous lesion on the right great toe in the other patient was a lentigo maligna melanoma. On fluorescence microscopy, characteristic findings of the pigment cells lying in the epidermis of both types may be summarized as follows: In the Pagetoid melanoma, the melanoma cells are ovoid, lack dendritic processes, and emit specific yellow fluorescence. In the lentigo maligna melanoma, the pigment cells clearly show dendritic processes, and emit specific green fluorescence.     

Clinical evaluation of cutaneous malignant melanoma with histologically involved lymph node metastases.

Thirty-six cases of cutaneous malignant melanoma with histologically involved lymph nodes were studied during a 2-10 year study period, and the characteristics of the metastasized nodes and the associated prognosis were compared. The results were as follows: 1) the survival rate in cases with 3 or fewer (n = 16) metastasized nodes was significantly higher than in cases with 4 or more positive nodes (n = 20); 2) the survival rate in cases in which metastasized nodes were limited to one regional lymph node section (n = 12) was significantly higher than in cases where metastasis extended to two or more intra-regional sections of nodes (n = 24); 3) cases which had nodes measuring 3.00 cm or less (n = 25) had significantly higher survival rates than those with nodes of 3.01 cm or more (n = 11). Therefore, the results indicate that the number of metastasized lymph nodes, the extension into regional lymph node sections, and the size of the metastasized lymph node(s) can be considered as important prognostic factors for melanoma patients.     

Pedunculated melanoma with pulmonary and bony metastases

We report a patient with pedunculated melanoma. Rounded and epithelioid-type melanoma cells had proliferated in the epidermis and massively into the deep dermis in the pedunculated nodule. At the base of the pedicle, lengtiginous-type melanoma cells formed nests of various sizes in the epidermis extending ten or more rete ridges beyond the site of invasion. Thus, this case shows that a pedunculated melanoma is not necessarily a variant of nodular melanoma. Six years after the primary operation, late recurrence was detected in regional lymph nodes, and nine years after the initial operation, the patient was found to have three large metastatic nodules, up to 8.5 cm in longest diameter, in her lung and bone. Although she died six months after the metastasectomy, prompt surgical excision of the primary tumor and metastasectomy can provide longer survival.     

Immunohistochemical expression of p16 in desmoplastic melanoma

Desmoplastic melanoma can be difficult to distinguish from desmoplastic melanocytic nevi both clinically and histopathologically. Several attempts have been made to explore the use of ancillary studies to facilitate this distinction. Prior work has suggested that immunohistochemical expression of p16 could help distinguish sclerosing Spitz nevi from desmoplastic melanomas. We re‐evaluated the expression of p16 in 22 desmoplastic melanomas (13 mixed and 9 pure desmoplastic tumors) and five desmoplastic melanocytic nevi (three desmoplastic Spitz nevi and two congenital melanocytic nevi with prominent dermal sclerosis). All desmoplastic melanocytic nevi were strongly immunoreactive for p16. Of the 22 desmoplastic melanomas, 6 tumors failed to label for p16, 10 were focally positive, but 6 tumors were diffusely immunoreactive. The latter finding is relevant, as it points to limitations in the diagnostic value of immunohistochemical staining for p16 for the diagnosis of desmoplastic melanocytic proliferations. Diffuse staining for p16 is not restricted to desmoplastic Spitz nevi but can also occur in a subset of desmoplastic melanomas, and this warrants caution in the use of this marker for diagnostic purposes.     

Microarray analysis of phosphatase gene expression in human melanoma

BACKGROUND: Tyrosine phosphate is abnormally elevated in malignant melanoma, and this has been interpreted to reflect the activity of oncogenic protein tyrosine kinases. However, elevation may also arise due to decreased protein tyrosine phosphatase (PTP) expression. OBJECTIVES: To survey phosphatase gene expression in melanoma cell lines, a benign naevus and normal melanocytes: we searched for downregulation of phosphatase gene expression in malignant cells that may indicate a role as melanoma suppressor genes. METHODS: Microarray analysis was used to compare gene expression for 133 phosphatase genes, comprising 39 PTPs, 16 dual-specificity phosphatases (DSPs), 47 serine/threonine phosphatases and 31 acid/alkaline and lipid-based phosphatases. Northern blotting analysis was used to study gene expression in human melanoma biopsies. RESULTS: There was decreased expression of four DSP genes (including PTEN); eight receptor PTP genes were downregulated in melanoma, among which were PTP-KAPPA and PTP-PI (consistent with our previous data). In addition, PTP-RF/LAR was downregulated in 13 of 22 metastatic melanomas. CONCLUSIONS: The expression of multiple PTP receptors is decreased in melanoma; this may be a mechanism which stimulates autonomous growth in advanced melanoma.     

Loss of beta-catenin expression associated with disease progression in malignant melanoma

BACKGROUND: beta-catenin plays a crucial role in the function of cell adhesion molecules and also participates in growth regulatory signalling pathways that may be involved in malignant transformation. OBJECTIVES: To examine beta-catenin expression in lesions of melanocytic origin for associations with clinicopathological markers of disease progression and for its significance as a predictor of disease recurrence and prognosis. METHODS: beta-catenin expression was examined by immunoperoxidase staining in 50 melanocytic naevi and 91 primary and 50 metastatic melanomas. RESULTS: beta-catenin was expressed in 96% of melanocytic naevi, in 94% and 65%, respectively, of radial and vertical growth phase primary melanomas, and in 38% of metastatic melanomas. Benign and malignant melanocytic lesions had distinct patterns of beta-catenin localization. Most lesions expressing beta-catenin exhibited cytoplasmic staining; however, over 40% of benign lesions also displayed nuclear staining, which was present only in 10% of primary and 15% of metastatic melanomas. Absent or weak expression of beta-catenin in primary melanomas was associated with several markers of disease progression, including tumour thickness and presence of lymph node metastases. A similar but not statistically significant trend was observed for the association of beta-catenin expression with disease recurrence and prognosis. CONCLUSIONS: These results suggest that loss or downregulation of beta-catenin expression in melanoma cells plays a significant role in progression of the disease.     

黑素瘤抑制性活性因子在黑素瘤不同阶段及基底细胞癌中的表达

目的：探讨黑素瘤抑制性活性因子（MIA）在黑素瘤及基底细胞癌中的表达及其作用。方法：应用sP免疫组化技术检测38份黑素瘤石蜡标本、35份基底细胞癌石蜡标本以及32份色素痣石蜡标本中MIA的表达水平。结果：MIA在所有色素痣以及基底细胞癌中均呈阴性表达，而在原位黑素瘤、侵袭性黑素瘤、有淋巴结转移的黑素瘤、无淋巴结转移的黑素瘤阳性表达率分别为21．4％、91．6％、94．1％和42．8％。结论：MIA在黑素瘤的发生发展中起重要作用，MIA有可能成为临床诊断、治疗黑素瘤的靶点。