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Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B(GPNMB)as a drug resis-tance and prognostic marker for non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)amplifica-tion accompanied by mutations.Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group.All patients received an EGFR-tyrosine kinase inhibitor(EGFR-TKI)as the first-line treatment;67 blood samples from the physical examination center during the same period were randomly included as healthy control.We compared the expression levels of free GPNMB between the two groups,explored the correlation between GPNMB expression and the clinicopathological information in the observation group;and combined the clinical efficacy to evaluate its value as a drug resistance marker.Through follow-up,the progress free survival(PFS)of patients was statistically analyzed,and through multivariate Cox regression analysis,independent risk factors affecting the survival in the observation group were explored.Results Compared with that in the control group,the expression level of free GPNMB in the observation group was signi-ficantly up-regulated.The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI(P = 0.016).Patients with high GPNMB expression have significantly stronger drug resistance,and patients with high GPNMB expression have significantly shorter PFS duration(P = 0.032).A high free GPNMB expression(HR = 4.029,95%CI:1.942-8.358,P<0.001)is also an independent risk factor affecting patient survival.Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated,and its high expression is significantly related to the enhancement of the patient's drug resistance.High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.
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OBJECTIVES@#To investigate the effects of injury time, postmortem interval (PMI) and postmortem storage temperature on mRNA expression of glycoprotein non-metastatic melanoma protein B (Gpnmb), and to establish a linear regression model between Gpnmb mRNA expression and injury time, to provide aimed at providing potential indexes for injury time estimation.@*METHODS@#Test group SD rats were anesthetized and subjected to blunt contusion and randomly divided into 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h groups after injury, with 18 rats in each group. After cervical dislocation, 6 rats in each group were collected and stored at 0 ℃, 16 ℃ and 26 ℃, respectively. The muscle tissue samples of quadriceps femoris injury were collected at 0 h, 12 h and 24 h postmortem at the same temperature. The grouping method and treatment method of the rats in the validation group were the same as above. The expression of Gpnmb mRNA in rat skeletal muscle was detected by RT-qPCR. The Pearson correlation coefficient was used to evaluate the correlation between Gpnmb mRNA expression and injury time, PMI, and postmortem storage temperature. SPSS 25.0 software was used to construct a linear regression model, and the validation group data was used for the back-substitution test.@*RESULTS@#The expression of Gpnmb mRNA continued to increase with the prolongation of injury time, and the expression level was highly correlated with injury time (P<0.05), but had little correlation with PMI and postmortem storage temperature (P>0.05). The linear regression equation between injury time (y) and Gpnmb mRNA relative expression (x) was y=0.611 x+4.489. The back-substitution test proved that the prediction of the model was accurate.@*CONCLUSIONS@#The expression of Gpnmb mRNA is almost not affected by the PMI and postmortem storage temperature, but is mainly related to the time of injury. Therefore, a linear regression model can be established to infer the time of injury.
Subject(s)
Animals , Rats , Glycoproteins , Linear Models , Melanoma , Membrane Glycoproteins/genetics , Postmortem Changes , Rats, Sprague-Dawley , RNA, Messenger/metabolism , Time FactorsABSTRACT
Objective:To analysis clinical and histopathological features of solitary dermal melanoma (SDM) .Methods:Clinical and histopathological data were collected from 5 patients with SDM, and analyzed retrospectively.Results:The 5 patients with SDM presented with black, skin-colored or red papules or nodules without any specific anatomic predilection. These lesions pathologically manifested as localized dermal/subcutaneous solitary nodules with characteristics of malignancy but no obvious capsules, and the epidermis was not involved.Conclusion:Detailed clinical data and skin histopathological examination are the key to accurate diagnosis of SDM.
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Although early stage melanoma can be cured by complete resection, the prognosis of the patients with unresectable or metastatic disease is dismal with the overall survival less than 1 year based on resistance to chemotherapeutic agents. Dacarbazine as either a single agent or in combination regimens with other cytotoxic agents has still remained as a standard in Korea for more than three decades although it has not been associated with any survival benefit for metastatic melanoma. Recently, according to advances in molecular science and immunology, the mechanisms responsible for biology of melanoma have been elucidated and then new agents targeting these mechanisms have been introduced leading survival benefit in patients with metastatic melanoma. Unfortunately, however, it is still difficult to give those new drugs to these patients in Korea because of the health insurance guidelines still defining dacarbazine as a front line regimen and moreover high cost and unavailability in the practice. Therefore, amendment of current guidelines and an in-depth discussion with the government for the earlier use of the novel drugs are strongly needed for the patients' sake.
Subject(s)
Humans , Antibodies, Monoclonal , Biology , Cytotoxins , Dacarbazine , Indoles , Insurance, Health , Korea , Melanoma , Prognosis , SulfonamidesABSTRACT
Although early stage melanoma can be cured by complete resection, the prognosis of the patients with unresectable or metastatic disease is dismal with the overall survival less than 1 year based on resistance to chemotherapeutic agents. Dacarbazine as either a single agent or in combination regimens with other cytotoxic agents has still remained as a standard in Korea for more than three decades although it has not been associated with any survival benefit for metastatic melanoma. Recently, according to advances in molecular science and immunology, the mechanisms responsible for biology of melanoma have been elucidated and then new agents targeting these mechanisms have been introduced leading survival benefit in patients with metastatic melanoma. Unfortunately, however, it is still difficult to give those new drugs to these patients in Korea because of the health insurance guidelines still defining dacarbazine as a front line regimen and moreover high cost and unavailability in the practice. Therefore, amendment of current guidelines and an in-depth discussion with the government for the earlier use of the novel drugs are strongly needed for the patients' sake.
Subject(s)
Humans , Antibodies, Monoclonal , Biology , Cytotoxins , Dacarbazine , Indoles , Insurance, Health , Korea , Melanoma , Prognosis , SulfonamidesABSTRACT
Objective To observe the expression of glycoprotein non-metastatic melanoma protein B (Gpnmb) in the kidney and urine after ischemic-reperfusion injury (IRI),and explore the relationship between Gpnmb and macrophage phenotypes in the IRI kidney.Methods Male C57BL/6J mice were randomly divided into control group (n =4),sham group (n =4) and IRI group (n =12).Both renal pedieles of mice in IRI group were identified and occluded with microvascular clamps for 30 min.Renal pathological injury was observed by PAS staining.The expression of Gpnmb was examined by real-time PCR and immunofluoresence staining.The location of Gpnmb was observed by flow cytometry and double immunofluoresence staining with F4/80.The mRNA expressions of Gpnmb,CD40,CRR7,CD163 and MMR were examined by real-time PCR.The expression of Gpnmb in the urine was examined by Western blotting and ELISA.Results PAS-stained IRI kidney section showed desquamative epithelia,necrosis debris and a large number of inflammatory cell infiltration.Real-time PCR results showed that there was little expression of Gpnmb in the kidney of control group and sham group.However,the Gpnmb mRNA level in IRI kidneys was highly up-regulated at day 1 and day 2 (both P < 0.01) and followed by a decrease that was similar to the control level at day 3.Double immunofluoresence staining of kidney sections from IRI mice revealed that Gpnmb was predominantly detected in F4/80 positive macrophages.The mRNA expression of Gpnmb was not correlated with M1 macrophage phenotypes CD40 and CCR7,but positively correlated with M2 macrophages phenotypes CD163 and MMR.Western blotting and ELISA result showed that there was significant increase of Gpnmb expression in the urine from IRI mice compared to those of the control group and the sham group (P < 0.01).Conclusions Gpnmb expression is up-regulated in IRI kidney and is associated to M2 macrophages.It may play a role in the process of acute kidney injury.Gpnmb expression is also increased in urine after IR injury and it may be a new biomarker to diagnose AKI.
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Large congenital melanocytic nevi (>20 cm in greatest diameter) are very rare and are seen in approximately 1 in 20,000 newborns. The major risk these patients face is the development of neurocutaneous melanosis or malignant melanoma. We report a rare case of large congenital melanocytic nevus with metastatic melanoma in a 40-year-old woman. In this case, though the primary was not established with certainty, on the basis of clinical course and radiological evaluation of various organs, we presume that the primary could be in the lung.
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Although malignant melanoma usually occurs after the diagnosis of vitiligo-like depigmentation, the latter is rarely followed by the former. We herein report on such a case in which recognition of the vitiligo-like depigmentation preceded diagnosing the metastatic melanoma by several months. A 56-year-old woman had first developed vitiligo-like depigmentation on the forehead, eyelids, neck and back 18 months previously and thereafter she detected a hard mass in the left axilla 2 months previously. Based on the histologic findings, the axillary mass was diagnosed as metastatic melanoma. To evaluate the primary tumor focus, thorough examinations that included PET-CT, bone scan and sigmoidoscopy were performed, but we couldn`t find any the original primary tumor. Our case suggests that the vitiligo-like depigmentation could be a sign that heralds metastatic melanoma.
Subject(s)
Female , Humans , Middle Aged , Axilla , Eyelids , Forehead , Melanoma , Neck , SigmoidoscopyABSTRACT
Patients with stage IV metastatic melanoma have been traditionally managed with mainly palliative therapy such as chemotherapy, radiation therapy or biologic therapy, yet their overall survival is unsatisfactory. Several recent series have indicated a long-term survival benefit after complete resection, (termed "metastasectomy") of distant metastatic foci in patients with metastatic melanoma. Unlike other palliative modalities, surgery like metastasectomy can rapidly render a patient clinically disease-free with rather minimal morbidity, a short-term of hospitalization and a quick recovery time. This may prolong the survival and improve the quality of life of patients with stage IV melanoma if all the clinicoradiologically-evident tumors can be completely resected. We report herein on a case of performing metastasectomy in a patient who had malignant melanoma with soft tissue metastasis of the breast (T3a/bN0M1a), even though there was a regrettable result.
Subject(s)
Humans , Biological Therapy , Breast , Hospitalization , Melanoma , Metastasectomy , Neoplasm Metastasis , Palliative Care , Quality of LifeABSTRACT
A metastatic melanoma to the gastrointestinal tract is observed in 1.5~4.4% of all melanoma patients. However, colonic and rectal involvement is less common. A 72-year-old woman was admitted due to abdominal pain and poor oral intake for 20 days. She had a 3 x 4 cm-sized mass on her right inguinal area 4 month ago, which was diagnosed as a malignant melanoma of the inguinal lymph node on excision biopsy. A large exophytic mass with an irregular ulcerlated, whitish patch, erythematous surface was observed in the hepatic flexure during colonoscopy. A histology diagnosis of a metastatic melanoma was made by an optical microscopy examination of the biopsies obtained during the colonscopy, and palliative right hemicolectomy was performed on account of a potential intestinal obstruction. We report a case of a metastatic melanoma of the colon with a review of the relevant literature.
Subject(s)
Aged , Female , Humans , Abdominal Pain , Biopsy , Colon , Colonoscopy , Diagnosis , Gastrointestinal Tract , Intestinal Obstruction , Lymph Nodes , Melanoma , MicroscopyABSTRACT
A 31-year old woman had been diagnosed as a metastatic melanoma of unknown origin 7 month before. Multiple cutaneous nodules had developed about 2 months before. When she visited our dermatologic clinic, the number of cutaneous nodules was increased and her urine was dark-brown colored. Histopathologically, the cutaneous nodule had typical for metastatic melanoma. After cytospin of her urine, we observed melanin dusts within macrophage on Fontana-Masson stain. This is a rare case showing melanuria.
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Adult , Female , Humans , Dust , Macrophages , Melanins , Melanoma , Neoplasm MetastasisABSTRACT
Malignant melanoma is a neoplasm of the skin and mucous membrane. Extragenital malignant melanoma that metastasizes to the ovary is seen rarely, and in only a few cases has the diagnosis been made before autopsy. The most common histologic feature that should raise the question of metastatic melanoma is the presence of numerous epitheloid cells with abundant eosinophilic cytoplasm. Despite advances in chemotherapy and immunotherapy the efficacy of treatment of advanced melanoma remains limited and the prognosis of metastatic disease remains guarded. We describe a case of malignant melanoma metastatic to the ovary and right axillae occurring one year and four months after diagnosis of cutaneous malignant melanoma on the patient's back.
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Female , Autopsy , Axilla , Cytoplasm , Diagnosis , Drug Therapy , Eosinophils , Immunotherapy , Melanoma , Mucous Membrane , Ovary , Prognosis , SkinABSTRACT
Although the characteristic cytologic features of melanoma have been well described, the diagnosis of metastatic melanoma by fine needle aspiration cytology (FNAC) may be difficult in the case of amelanotic melanoma and in the absence of awareness of clinical history. Furthermore, when the breast is the site of initial presentation, it could simulate a primary breast carcinoma leading to misdiagnosis. The recognition of metastatic malignant melanoma in FNAC material is essential to avoid an unnecessary mastectomy and to ensure appropriate chemotherapy. We experienced a case of metastatic melanoma of breast which presented as solitary breast mass in a 56-year-old woman. She had a history of surgical excision of right foot for melanoma one year ago. The cytologic smears were composed of noncohesive epithelioid cells with round or eccentric nuclei, bi-or multi-nucleation, prominent nucleoli, fine chromatin, and intranuclear inclusions. The cytoplasm of tumor cells had scanty melanin pigment but were diffusely positive for S-100 protein.
Subject(s)
Female , Humans , Middle Aged , Biopsy, Fine-Needle , Breast Neoplasms , Breast , Chromatin , Cytoplasm , Diagnosis , Diagnostic Errors , Drug Therapy , Epithelioid Cells , Foot , Intranuclear Inclusion Bodies , Mastectomy , Melanins , Melanoma , Melanoma, Amelanotic , S100 ProteinsABSTRACT
A case of thoracic epidural malignant melanoma metastasized from the eyeball is presented. The patient is a 28 year old male with the chief complaint of paraparesis. He underwent laminectomy and gross total removal of the mass Chemotherapy was thean administered postoperatively. The literature on this subject is briefly reviewed.
Subject(s)
Adult , Humans , Male , Drug Therapy , Epidural Space , Laminectomy , Melanoma , Orbit , ParaparesisABSTRACT
Metastatic melanoma is often difficult to diagnose morphologically. However, the prognostic and therapeutic decision in cases of metastatic melanoma depends upon the morphologic documentation of the metastatic disease, which may rapidly and accurately be done by cytologic methods such as aspiration cytology of clinically suspicious lesion. Cytological features of 12 metastatic melanoma are described. Evaluation for melanin pigment, background composition, cytoplasmic vacuoles, intranuclear inclusions, bi or multinucleated cells, eccentric nuclei, nucleoli, and degree of cellular cohesion were made. the presence of melanin pigment, prominent nucleoli, intranuclear cytoplasmic inclusions, lack of cell cohesion, and eccentric nuclei are the important and useful cytologic features in the diagnosis of metastatic melanoma. Bior multinucleated cells, cytoplasmic vacuoles, and bloody background are also frequently found in smears from metastatic melanoma.
Subject(s)
Cytoplasm , Diagnosis , Inclusion Bodies , Intranuclear Inclusion Bodies , Melanins , Melanoma , VacuolesABSTRACT
Objective: To investigate the role and mechanism of histamine in regulation of C57BL/6 mice spleen derived LAK activity in vivo. Methods: The C57BL/6 mice carrying B16 pulmonary metastatic melanoma were treated with LAK/IL 2/histamine therapy or LAK/IL 2 therapy with the aim of evaluating both anti tumor responses in vivo. Results: It was found that the addition of histamine effectively potentiated the anti metastatic effect produced by LAK/IL 2 therapy and induced regression of NK resistant B16 pulmonary metastatic melanoma. Survival period was significantly prolonged in mice receiving LAK/IL 2/histamine as compared with LAK/IL 2 therapy alone. The effect of histamine was completely blocked by H 2 R antagonist ranitidine, and mimicked by dimaprit, a H 2 R agonist. Conclusion:Histamine, via specific activation of H 2 R, may be an important regulator of LAK cells activity; histamine and LAK/IL 2 synergistically induce more potent antitumor efficacy in vivo .