Characteristics of the patients with cutaneous melanoma and multiple primary malignant tumors: clinical observations

Background. Multiple primary malignant tumors (MPMT) - 2 or more tumors, arising during patient life - are an important risk factor of cutaneous melanoma (CM). The frequency of MPMT in Russia ranges from 2 to 20 % with the incidence increasing. This tendency is linked mainly with the increasing life expectancy of the patients, with use of a potentially carcinogenic treatment methods, with the influence of adverse environmental factors and genetic predisposition In 15 patients with MPMT, including CM, has revealed a trend towards more frequent family history in male patients. In female patients MPMT included breast, ovarian and renal malignant tumors. CM relapses were observed shortly after surgical removal of the primary tumors. Objective. Clinical and genetic characteristics of patients with MK in MPMT structure. Materials and methods. Disease histories, MPMT structure and CM mutational status (PCR followed by direct sequencing of amplions) were analyzed in 8 male and 7 female patients with MPMT included metastatic CM. Results. A preliminary analysis of 15 patients with metastatic CM in MPMT structure has revealed some gender features. In female patients MPMT more often included breast, ovaries or kidney tumors. Excess body weight or obesity was detected in female patients (5/7) more often than in male patients (4/8). There is a tendency to more frequent family cancer histories in male patients compared to female ones - 3/8 vs. 1/7 in 3/8 male patients somatic mutations in BRAF gene (2) and PDGF gene (1) were identified in CM. The frequency of mutations of BRAF and NRAS genes in CM of female patients was 2 times higher than that of male patients. The combination of CM with bowel cancer was prevalent in male patients. In 2/7 male patients CM was the last tumor in MPMT structure, in 5/7 - the first, with the exception of the patient with primary multiple melanomas, while CM as the first tumor was revealed in 4/7 female patients and last CM - in 1/7 ones. Conclusions. Various combinations of tumors in MPMT structure were characterized in male and female patients. In female patients MPMT included breast, ovarian and renal malignant tumors/were the most frequent, while the combination CM with bowel tumors were prevalent in male ones. In male patients CM was diagnosed as the first tumor more frequently than the last one. The frequency of mutations in BRAF and NRAS genes in MK tumors in female patients with MPMT was 2 times higher than that in male patients. In 15 patients with MPMT, including CM, a trend towards more frequent family cancer history in male patients was revealed. CM relases were observed shortly after surgical removal of the primary tumor.

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Dual-procedural separation of CTCs in cutaneous melanoma provides useful information for both molecular diagnosis and prognosis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920905415 ◽

2020 ◽

Vol 12 ◽

pp. 175883592090541 ◽

Cited By ~ 2

Author(s):

Marco Tucci ◽

Stella D’Oronzo ◽

Francesco Mannavola ◽

Claudia Felici ◽

Domenica Lovero ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Epithelial To Mesenchymal Transition ◽

Stage Iv ◽

Digital Pcr ◽

Isolated Cells ◽

Primary Tumors ◽

Mesenchymal Transition ◽

Diagnosis And Prognosis ◽

Mutational Status ◽

Magnetic Sorting

Background: Circulating tumor cells (CTCs) have recently emerged as a new dynamic soluble marker for several malignancies including cutaneous melanoma (CM) and are suitable for prognostic evaluations and treatment monitoring. However, to date many limitations still hamper the wide-scale application of CTCs in CM setting, including the lack of standardized methods as well as both low levels and heterogeneity of these cells. Methods: We developed a protocol for CTC detection in CM based on immune-magnetic sorting to deplete CD45-, CD31- or CD34-positive cells, followed by dielectrophoretic DEPArray separation according to cell morphology and immunophenotype. To this end, we explored the expression of melanoma stem cell antigens (CD271, ABCB5, and RANK) and the epithelial-to-mesenchymal transition markers (N-Cad, -CD44, and -MCAM/CD146) on CTCs from 17 stage IV CM patients, and investigated their BRAF mutational status by droplet digital PCR. Results: The number of CTCs isolated from CM patients ranged from 2 to 91 cells (38 ± 6.4) with respect to healthy donors ( p < 0.0002). To confirm the melanoma origin of isolated cells, we observed an 80% agreement between their BRAFV600 mutational status and matched primary tumors. The characterization of the immune phenotype of isolated cells revealed high interindividual and intraindividual heterogeneity that was found to correlate with the clinical outcome. Conclusions: The dual-step protocol of immune-magnetic sorting and subsequent dielectrophoretic DEPArray separation, turned out to be a suitable method to isolate viable CTCs from stage IV melanoma patients and enabled quantitative and qualitative analyses on these cells, which may deserve prospective evaluation for potential use in the clinical practice.

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Gender and survival benefit from initial irinotecan in metastatic colorectal cancer: Analysis of the XELAVIRI (AIOKRK0110) study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3559 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3559-3559 ◽

Cited By ~ 1

Author(s):

Kathrin Heinrich ◽

Dominik Paul Modest ◽

Ingrid Ricard ◽

Ludwig Fischer von Weikersthal ◽

Thomas Decker ◽

...

Keyword(s):

Objective Response ◽

Progression Free Survival ◽

Time To Failure ◽

Female Patients ◽

Strong Trend ◽

Mutational Status ◽

Full Analysis ◽

Male Patients ◽

Status Interaction ◽

And Gender

3559 Background: XELAVIRI compared initial vs sequential irinotecan (iri) in combination with fluoropyrimidine (FP) plus bevacizumab (bev) in patients (pts) with mCRC, trial identification: NCT01249638. In the full analysis set of the study, non-inferiority of time to failure of strategy (TFS) was not shown (primary endpoint). Pts with RAS/BRAF wildtype (wt) tumors benefitted from initial iri. Methods: The study endpoints objective response rate (ORR), progression-free survival (PFS), time to failure of strategy (TFS) as well as overall survival (OS) were evaluated in female vs. male pts as well as molecular subgroups (i.e. RAS mutational status). Interaction of treatment and gender was tested by likelihood ratio tests. Results: Of 421 patients, 281/140 were male/female. In male patients, ORR was 33.6% without and 58.3% with initial iri (P < 0.001). PFS (HR: 0.54 (95%CI 0.42-0.69) P < 0.001) and OS (HR: 0.63 (95%CI 0.47-0.85), P = 0.002), were also significantly better with initial iri. In the subgroup analysis, this effect was especially pronounced in pts with RAS/BRAF wt tumors. In female pts, ORR was 43% in both arms, PFS was similar (HR: 1.09 (95%CI 0.76-1.55), P = 0.65) without and with initial iri. In OS, a strong trend for inferior outcome with initial iri was seen (HR: 1.46 (95%CI 0.95-2.24), P = 0.08) that reached significance in the multivariate analysis (HR: 1.73 (95%CI 1.04-2.86, P = 0.034). Female patients with RAS/BRAF wt tumors did not benefit from initial iri (HR 1.05 (95% CI 0.46-2.41), P = 0.903 for OS). Formal interaction of treatment and gender was seen for ORR (P = 0.018), PFS (P = 0.002) and OS (P = 0.001). There were some trends for more pronounced toxicities in female pts treated with Irinotecan. Conclusions: This unplanned exploratory analysis suggests that gender might interact with efficacy of initial iri when used in the context of FP and bev. While especially male RAS wild-type patients derived a significant and clinically meaningful benefit from initial use of iri, this was not observed in female patients with RAS wt tumors. Clinical trial information: NCT01249638.

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LINE-1 hypomethylation and mutational status in cutaneous melanomas

Journal of Investigative Medicine ◽

10.1136/jim-2016-000066 ◽

2016 ◽

Vol 64 (4) ◽

pp. 899-904 ◽

Cited By ~ 7

Author(s):

Dimitrius T Pramio ◽

Paula C Pennacchi ◽

Silvya S Maria-Engler ◽

Antônio H J F M Campos ◽

João P Duprat ◽

...

Keyword(s):

Dna Methylation ◽

Cutaneous Melanoma ◽

Surrogate Marker ◽

Clinicopathological Characteristics ◽

Driver Mutations ◽

Primary Tumors ◽

Promoter Sequences ◽

Mutational Status ◽

Dna Elements ◽

Dependent Probe

Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation. In this work, LINE-1 methylation levels were evaluated in cutaneous melanomas and normal melanocyte primary cell cultures to investigate their possible association with both distinct clinicopathological characteristics and tumor mutational profile. A set of driver mutations frequently identified in cutaneous melanoma was assessed by sequencing (actionable mutations in BRAF, NRAS, and KIT genes, and mutations affecting the TERT promoter) or multiplex ligation-dependent probe amplification (MLPA) (CDKN2A deletions). Pyrosequencing was performed to investigate the methylation level of LINE-1 and CDKN2A promoter sequences. The qualitative analysis showed a trend toward an association between LINE-1 hypomethylation and CDKN2A inactivation (p=0.05). In a quantitative approach, primary tumors, mainly the thicker ones (>4 mm), exhibited a trend toward LINE-1 hypomethylation when compared with control melanocytes. To date, this is the first study reporting in cutaneous melanomas a possible link between the dysregulation of LINE-1 methylation and the presence of driver mutations.

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Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

10.21203/rs.3.rs-35299/v2 ◽

2020 ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications.Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n=349), as well as in male patients without BRCAm (n=4577).Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8% and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males.Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

10.21203/rs.3.rs-35299/v3 ◽

2020 ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

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Experience in the treatment of primary malignant tumors (retinoblastoma and osteosarcoma): analysis of the clinical case

Bone and soft tissue sarcomas, tumors of the skin ◽

10.17650/2070-9781-2021-13-2-36-43 ◽

2021 ◽

Vol 13 (2) ◽

pp. 36-43

Author(s):

A. A. Zagidullina ◽

V. Kh. Kharbediya ◽

A. Z. Dzampaev ◽

D. V. Nisichenko ◽

S. N. Mikhailova

Keyword(s):

Risk Factors ◽

Malignant Tumors ◽

Treatment Protocol ◽

Patient Treatment ◽

Special Treatment ◽

Primary Tumors ◽

Secondary Tumor ◽

Multiple Primary Tumors ◽

Multiple Primary ◽

The Impact

Background. Retinoblastoma is a malignant intraocular tumor developing from the retinal neuroectoderm and diagnosed primarily in young children. This type of cancer is associated with a high risk of multiple primary tumors emerging after treatment completion. Multiple primary tumors are two or more independent tumors developing in one patient. Treatment of this disease is challenging.Objective – to evaluate the impact of risk factors on the efficacy of therapy for multiple primary tumors and to analyze treatment outcomes.Materials and methods. A 2-year-old boy was diagnosed with bilateral retinoblastoma (OD – stage T3bN0M0 and OS – stage T3cN0M0). He received special treatment from September 2005 to November 2006. In 2012, the patient underwent cataract surgery: the lens was removed, then an intraocular lens was installed, and laser dissection of the posterior capsule of the lens was performed. Six years later, in August 2018, the patient was diagnosed with osteosarcoma. The boy received combination organ-sparing therapy according to the EURAMOS-1 treatment protocol for osteosarcoma. During therapy, he developed a secondary tumor, namely osteoblastic osteosarcoma. Both the boy and his father were found to have a mutation in the RB1 gene.Results. Currently, patient’s condition is satisfactory; he has no complains. The boy is in remission for 2 years.Conclusion. The development of secondary tumors depends on the genetic factors, type of treatment for primary tumor, and environmental factors. Therefore, it is extremely important to assess risk factors for multiple primary tumors at the moment of primary retinoblastoma detection. The results of such assessment will help to choose an optimal treatment strategy.

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Multiple primary tumors, especially malignant

Kazan medical journal ◽

10.17816/kazmj77674 ◽

1927 ◽

Vol 23 (12) ◽

pp. 1288-1288

Keyword(s):

Malignant Tumors ◽

Primary Tumors ◽

Multiple Primary Tumors ◽

Multiple Cancers ◽

Multiple Primary ◽

Primary Origin

The author reports that 9,371 autopsies performed between 1920 and 1926 at the Pathologoanat. The author reports that from the total number of cases of malignant tumors of 1.123 (11.98%) in the Institute of Pathology and Anatomy of Prof. Kiml in Prague 14 multiple cancers were found. Besides 4 cases in which the primary origin of the tumor was questionable, 10 cases (0,107% of all autopsies and 0.89% of malignant tumors) remain, where the primary plurality may be considered as reliable or at least very probable.

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Clinical characteristics and prognostic implications of BRCA-associated tumors in males: a pan-tumor survey

BMC Cancer ◽

10.1186/s12885-020-07481-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications. Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n = 349), as well as in male patients without BRCAm (n = 4577). Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8 and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males. Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

10.21203/rs.3.rs-35299/v4 ◽

2020 ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications. Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n=349), as well as in male patients without BRCAm (n=4577). Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8% and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males. Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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Multiple Primary Tumors Originating From the Prostate and Colorectum A Clinical-Pathological and Therapeutic Challenge

American Journal of Men s Health ◽

10.1177/15579883211044881 ◽

2021 ◽

Vol 15 (5) ◽

pp. 155798832110448

Author(s):

Sorin Dema ◽

Andreea Bota ◽

Sorina Maria Tăban ◽

Adelina Gheju ◽

Alis Liliana Carmen Dema ◽

...

Keyword(s):

Medical Records ◽

Malignant Tumors ◽

Synchronous Tumors ◽

Primary Tumors ◽

Oncologic Patients ◽

Multiple Primary ◽

Reference Hospital ◽

The Mean ◽

Personalized Approach ◽

Metachronous Tumors

Considering that the incidence of colorectal (CRC) and prostatic cancer (PC) increases with age, metachronous and synchronous tumors can often affect the same patient. Despite the importance of this subject for the diagnosis and management of oncologic patients, in medical literature the data are scarce. The aim of the study was to evaluate the incidence and the characteristics of double/multiple primary malignant tumors (D/MPMTs) with colorectal and prostatic origin, in patients admitted to a reference hospital in West Romania. A 4-year retrospective observational study (2016–2019) was conducted by analyzing the medical records of all patients admitted in the hospital. Demographic and clinical data, as well as tumor-related parameters, were extracted. We identified 413 consecutive hospitalized patients with PC, and 21 (5%) of them also had a primary CRC. At the time of diagnosis, the mean age of the patients with PC was 71.2 ± 6 years, and 71.8 ± 10 years for patients with CRC. Synchronous PC and CRC tumors were identified in 3/21 cases and metachronous tumors in 18/21 cases. Prostate cancer was the first tumor to be diagnosed in 13/18 cases and CRC in 5/18 cases. The most frequent subtype of PC was acinar adenocarcinoma (90%) and for CRC cases, conventional adenocarcinoma (90%). Prostate and colorectal cancers tend to co-occur in a single patient. The diagnosis of one of these two types of tumors should imply the screening for the other one, because these patients require a multidisciplinary and personalized approach.

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