scholarly journals Expression of SEC62 Oncogene in Benign, Malignant and Borderline Melanocytic Tumors—Unmasking the Wolf in Sheep’s Clothing?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1645
Author(s):  
Cornelia S. L. Müller ◽  
Claudia Pföhler ◽  
Maria Wahl ◽  
Florian Bochen ◽  
Sandrina Körner ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Tumor Biology ◽  
Hepatocellular Cancer ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Biological Behavior ◽  
Melanocytic Tumors ◽  
Melanocytic Lesions ◽  
Spitz Nevi ◽  
N 93

SEC62 oncogene located at chromosomal region 3q26 encodes for a transmembrane protein of the endoplasmic reticulum (ER) and is expressed at high levels in numerous human malignancies. SEC62 overexpression has been associated with worse prognosis and high risk for lymphatic and distant metastases in head and neck cancer, cervical cancer, hepatocellular cancer, and lung cancer. However, its role in the development and tumor biology of melanocytic lesions has not been investigated so far. An immunohistochemical study including 209 patients with melanocytic lesions (malignant melanoma (MM), n = 93; melanoma metastases (MET), n = 28; Spitz nevi (SN), n = 29; blue nevi (BN), n = 21; congenital nevi (CN), n = 38) was conducted and SEC62 expression was correlated with clinical data including patient survival and histopathological characteristics. SN showed the highest SEC62 expression levels followed by MET, MM, CN, and BN. High SEC62 expression correlated with a shorter overall and progression-free survival in MM patients. Additionally, high Sec62 levels correlated significantly with higher tumor size (T stage), the presence of tumor ulceration, and the presence of lymph node as well as distant metastases. Strikingly, SEC62 expression showed a strong correlation with Clark level. Taken together, these data demonstrate that SEC62 is a promising prognostic marker in MM and has the potential to predict biological behavior and clinical aggressiveness of melanocytic lesions.

scholarly journals Role of CALLA/CD10 Expression in Progression of Melanocytic Tumors: A Study in Egypt

2021 ◽  
Vol 9 (A) ◽  
pp. 164-168
Author(s):  
Maha Elsayed Mohammed Salama ◽  
Dina Ahmad Khairy
Keyword(s):  
Ulcer Formation ◽  
Ki67 Expression ◽  
Melanocytic Tumors ◽  
Melanocytic Lesions ◽  
Potential Biomarker ◽  
Spitz Nevi ◽  
Cd10 Expression ◽  
The Difference ◽  
Benign Melanocytic Nevi

BACKGROUND: Although most of melanocytic lesions can be diagnosed using morphology, there is a significant subset of lesions that are difficult to diagnose. These are a source of anxiety for patients, clinicians, and pathologists. This arouses the possible benefits of using ancillary techniques to solve this problem. CD10 is a zinc-dependent metalloproteinase, its expression is known to be associated with biological aggressiveness in various malignancies. AIM: This research observes the efficacy of CD10 in the progression of melanocytic tumors as well as the differential diagnosis between nevus and melanoma. METHODS: The material of this study included 49 paraffin blocks of Egyptian melanocytic tumors. CD10 expression either membranous and/or cytoplasmic in tumor cells was considered positive and scored, based on the percentage of cells stained and compared to Ki67 expression as a prognostic marker. RESULTS: In benign melanocytic nevi, only 16.7% of cases showed positive expression, all were + 1 score, compared to 82.6% of melanoma cases, mostly +1 score followed by +3 score and finally +2 score. The difference in CD10 expression among melanocytic tumors showed a highly statistically significant correlation between nevus and melanoma cases as well as in Spitz nevi versus other nevi. Another highly statistically significant correlation was observed between CD10 expression and both Ki67 expression and ulceration. CONCLUSION: CD10 expression was significantly higher expressed in melanomas rather than nevi with highly statistically significant positive relation with Ki67 and ulcer formation which supports its role as a potential biomarker in the development of malignant melanoma and marker of aggression.

scholarly journals Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors

2020 ◽  
Vol 18 (10) ◽  
pp. 1327-1336
Author(s):  
Andrea Maurichi ◽  
Rosalba Miceli ◽  
Roberto Patuzzo ◽  
Francesco Barretta ◽  
Gianfranco Gallino ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Sentinel Node ◽  
Sentinel Node Biopsy ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Mitotic Rate ◽  
Free Survival ◽  
Melanocytic Tumors ◽  
Node Biopsy

Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. Patients and Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. Results: Median follow-up was 126 months (interquartile range, 104–157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node–negative and 3 patients who were sentinel node–positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%–99.2%) and 82.2% (95% CI, 77.3%–87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. Conclusions: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.

scholarly journals Targeted Sequencing Revealed Distinct Mutational Profiles of Ocular and Extraocular Sebaceous Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4810
Author(s):  
Hee Young Na ◽  
Jeong Hwan Park ◽  
Sun Ah Shin ◽  
Sejoon Lee ◽  
Heonyi Lee ◽  
...  
Keyword(s):  
Genetic Background ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Genetic Alterations ◽  
Sebaceous Carcinoma ◽  
Biological Behavior ◽  
Free Survival ◽  
Targeted Next Generation Sequencing ◽  
Repair Genes ◽  
Generation Sequencing

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

scholarly journals Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Objective Response ◽  
Case Series ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
First Line ◽  
Pleomorphic Sarcoma ◽  
Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

scholarly journals Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer

2021 ◽  
Author(s):  
Tilman D. Rachner ◽  
Sabine Kasimir-Bauer ◽  
Andy Goebel ◽  
Kati Erdmann ◽  
Oliver Hoffmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Poor Prognosis ◽  
Therapeutic Potential ◽  
Transmembrane Protein ◽  
Tumor Biology ◽  
Tumor Stage ◽  
Her2 Status ◽  
Tyrosine Kinase Receptor ◽  
Neuropilin 1

Abstract Background Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies. Materials and methods We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA. Results Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23–3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09–2.91). Conclusion Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.

Cetuximab Plus Irinotecan in Heavily Pretreated Metastatic Colorectal Cancer Progressing on Irinotecan: MABEL Study

2008 ◽  
Vol 26 (33) ◽  
pp. 5335-5343 ◽  
Author(s):  
Hansjochen Wilke ◽  
Robert Glynne-Jones ◽  
Josef Thaler ◽  
Antoine Adenis ◽  
Peter Preusser ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Practice Setting ◽  
Community Practice ◽  
Efficacy And Safety ◽  
Intention To Treat ◽  
Heavily Pretreated ◽  
N 93

Purpose This large, multinational study aimed to confirm in a community practice setting the efficacy and safety of cetuximab plus irinotecan in patients with epidermal growth factor–expressing metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen. Patients and Methods The primary objective was to determine the progression-free survival (PFS) rate at 12 weeks. The initial cetuximab dose was 400 mg/m2 and was followed weekly by 250 mg/m2; irinotecan (according to prestudy regimen) was given weekly (125 mg/m2 weekly for 4 of 6 weeks), every 2 weeks (180 mg/m2 each), or every 3 weeks (350 mg/m2 each). Results The intention-to-treat/safety population comprised 1,147 treated patients who received irinotecan weekly (n = 93); every 2 weeks (n = 670); every 3 weeks (n = 356); or another dose (n = 28). The PFS rate at 12 weeks was 61%, and the median survival was 9.2 months. Treatment was generally well tolerated. The most common treatment-related grades 3 to 4 adverse events were diarrhea (19%), neutropenia (10%), rash (7%), and asthenia (6%). The rate of grades 3 to 4 infusion-related reactions (IRRs; composite adverse event category) was 1% for patients who received both antihistamine and corticosteroid premedication. Conclusion Tolerability (except IRR incidence), PFS rate, and overall survival rate were in line with previous results. At 1%, the rate of IRRs in patients who received prophylactic premedication with both antihistamine and corticosteroid is lower than previously reported. MABEL clearly confirms in a community practice setting the efficacy and safety of cetuximab plus irinotecan in the treatment of mCRC.

scholarly journals Expanding spectrum of “spitzoid” lesions: a small series of 4 cases with MAP2K1 mutations

2020 ◽  
Author(s):  
K. G. P. Kerckhoffs ◽  
T. Aallali ◽  
C. A. Ambarus ◽  
V. Sigurdsson ◽  
A. M. L. Jansen ◽  
...  
Keyword(s):  
Significant Proportion ◽  
Malignant Potential ◽  
Low Grade ◽  
Superficial Spreading ◽  
Activating Mutations ◽  
Distinct Phenotype ◽  
Melanocytic Tumors ◽  
Melanocytic Tumor ◽  
Small Series ◽  
Spitz Nevi

Abstract The molecular background of a significant proportion of spitzoid neoplasms is still unknown. Recently, activating mutations in MAP2K1 have been described in a few spitzoid lesions, but not in benign Spitz nevi. We report four cases of melanocytic tumors with spitzoid features in which a MAP2K1 mutation was detected. The lesions did not show a single distinct phenotype and ranged from benign to malignant. Two cases resembled desmoplastic Spitz nevi. Based on the combination of morphological, immunohistochemical, and molecular findings, one case was classified as benign, one as probably benign, possibly intermediate low-grade (MELTUMP—melanocytic tumor of unknown malignant potential), one case was classified as intermediate (MELTUMP), and one case was considered a superficial spreading melanoma with spitzoid features. Based on this, we conclude that MAP2K1 mutations can indicate a spitzoid genetic signature and can be found in both benign and malignant spitzoid neoplasms.

A clinical comparison between dedifferentiated low-grade osteosarcoma and conventional osteosarcoma

2019 ◽  
Vol 101-B (6) ◽  
pp. 745-752 ◽  
Author(s):  
S. Toki ◽  
E. Kobayashi ◽  
A. Yoshida ◽  
K. Ogura ◽  
S. Wakai ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Poor Response ◽  
Distant Metastases ◽  
Histological Evaluation ◽  
Low Grade ◽  
Cyclin Dependent Kinase ◽  
Free Survival ◽  
Standard Chemotherapy Regimen ◽  
Conventional Osteosarcoma ◽  
High Grade Osteosarcoma

Aims The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. Patients and Methods We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. Results The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. Conclusion Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745–752.

scholarly journals Atypical manifestation of parathyroid carcinoma with late-onset distant metastases

2017 ◽  
Vol 2017 ◽  
Author(s):  
Marina Tsoli ◽  
Anna Angelousi ◽  
Dimitra Rontogianni ◽  
Constantine Stratakis ◽  
Gregory Kaltsas
Keyword(s):  
Parathyroid Carcinoma ◽  
Late Onset ◽  
Tumor Biology ◽  
Elevated Serum ◽  
Specific Treatment ◽  
Distant Metastases ◽  
List Type ◽  
Parathyroid Cancer ◽  
Laboratory Findings ◽  
The Right

Summary Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment. Learning points: Metastases can develop many years after parathyroid cancer diagnosis. Surgery is the only curative treatment for parathyroid carcinoma. Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment. Patient registering is required in order to delineate underlining pathology and offer specific treatment.

scholarly journals Salvage radiotherapy for second oligo-recurrence in patients with breast cancer

2017 ◽  
Vol 59 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Mari Miyata ◽  
Takayuki Ohguri ◽  
Katsuya Yahara ◽  
Shinsaku Yamaguchi ◽  
Hajime Imada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Objective Response ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Distant Metastases ◽  
Salvage Radiotherapy ◽  
Severe Toxicity ◽  
Term Survival ◽  
Grade 3

Abstract A new concept designated ‘oligo-recurrence (OR)’ has been proposed, which indicates one to several distant metastases/recurrences in one or more organs, which can be treated with local therapy, after the primary site of the cancer has been controlled. The purpose of this study was to assess the efficacy and toxicity of salvage radiotherapy (RT) for the second OR of breast cancer. The second OR was defined as once-salvaged patients with OR who had a second failure that was also detected as the state of OR. Twenty-one patients with second OR were treated with salvage RT and were retrospectively analyzed. The sites of the second OR were locoregional recurrence in 7 patients and distant metastasis in 14 patients. Salvage RT was performed at a median total dose of 60 Gy. Nineteen (90%) patients had an objective response. The median overall survival and progression-free survival (PFS) times were 41 and 24 months after salvage RT for the second OR, respectively. The 3-year local (in-field) control (LC) rates were 93%. The toxicities were mild; acute toxicities ≥Grade 3 were seen in one patient with Grade 3 dermatitis, and no late toxicity ≥Grade 2 was observed. In conclusion, salvage RT for the second OR was able to achieve a better LC rate and longer PFS time without inducing severe toxicity, and therefore may be a potentially effective modality for inducing long-term survival in select patients.

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