Clinicopathological Characteristics of BRAF V600E Mutated Melanomas in the Dalmatian Region of Croatia

A high proportion of cutaneous melanomas harbor activating mutations of the BRAF or NRAS genes, which are components of mitogen-activated protein kinase (MAPK) signal transduction pathway. The importance of BRAF V600E mutation in melanoma is not only related to the possibility of the administration of the targeted therapy, but also to the fact that BRAF V600E mutated melanomas have distinct clinicopathological features. We investigated the clini-copathological features of 80 primary skin melanomas with known BRAF V600E mutation status excised in the Dalmatian region of Croatia, with comparison of these features between the mutated and wild-type group. The frequency of BRAF V600E mutation was 47.5%. In comparison with wild-type melanomas, BRAF V600E mutated melanomas were significantly associated with younger age and female sex (P=0.014 and P=0.011, respectively). The mutated melanomas were more often located on the extremities, of a nodular type, ulcerated, and with higher median of mitotic index but without significant difference in comparison with wild-type tumors. There were no differences in the depth of invasion and the presence of lymphovascular invasion, tumor infiltrating lymphocytes, and regression between the investigated groups. The frequency of BRAF V600E mutation in our cohort of primary skin melanomas and the clinicopathological features of mutated tumors were similar to those reported in the literature, except for the higher proportion of women observed in our group with mutation

Među-laboratorijska podudarnost HER-2 pozitivnih karcinoma dojke

Accurate assessment of HER -2 status is essential for identifying patients who will benefit from HER -2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER -2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinoma cases were HER -2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER -2 positive and 12% (17/143) as HER -2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER -2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as those from other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER -2 test results.Ispravna procjena HER -2 statusa je osnova za pronalaženje bolesnika kojima će koristiti HER -2 ciljana terapija. Cilj istraživanja je bio prikazati rezultate podudarnosti između testiranja HER -2 pozitivnih bolesnika oboljelih od raka dojke pri mjesnom i centralnom laboratoriju. U slučajevima nepodudarnih rezultata analize imunohistokemije (IH) i/ili in situ hibridizacije su se izvodile u centralnim laboratorijima. Ukupno 104 od 143 (72,72%) slučaja karcinoma dojke su bili HER -2 pozitivni (biljeg 3+), dok je skoro 14% tumora (20/43) prikazalo nisko (biljeg 2+) i 12% (19/143) negativno imunohistokemijsko bojenje (biljeg 0 i 1+). Nakon ponovljene analize IH i ISH 88% (126/143) se klasificiralo kao HER -2 pozitivni i 12% (17/143) kao HER -2 negativni slučajevi. Dobiveni rezultati su sukladni mnogim istraživanjima koja potvrđuju slične nepodudarnosti pri HER -2 testiranju imunohistokemijom i/ili FISH analizom između mjesnog i centralnog laboratorija. Prema tome, naši rezultati kao i rezultati drugih istraživanja podupiru značenje pravilnog procjenjivanja izvođenja protokola bojenja i dosljednosti interpretacija rezultata HER -2 testiranja

Interlaboratory concordance in HER-2 positive breast cancer

Accurate assessment of HER-2 status is essential for identifying patients who will benefit from HER-2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER-2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinomas cases were HER-2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER-2 positive and 12% (17/143) as HER-2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER-2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as of other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER-2 test results

Clinicopathological Characteristics of BRAF V600E Mutated Melanomas in the Dalmatian Region of Croatia

A high proportion of cutaneous melanomas harbor activating mutations of the BRAF or NRAS genes, which are components of mitogen-activated protein kinase (MAPK) signal transduction pathway. The importance of BRAF V600E mutation in melanoma is not only related to the possibility of the administration of the targeted therapy, but also to the fact that BRAF V600E mutated melanomas have distinct clinicopathological features. We investigated the clini-copathological features of 80 primary skin melanomas with known BRAF V600E mutation status excised in the Dalmatian region of Croatia, with comparison of these features between the mutated and wild-type group. The frequency of BRAF V600E mutation was 47.5%. In comparison with wild-type melanomas, BRAF V600E mutated melanomas were significantly associated with younger age and female sex (P=0.014 and P=0.011, respectively). The mutated melanomas were more often located on the extremities, of a nodular type, ulcerated, and with higher median of mitotic index but without significant difference in comparison with wild-type tumors. There were no differences in the depth of invasion and the presence of lymphovascular invasion, tumor infiltrating lymphocytes, and regression between the investigated groups. The frequency of BRAF V600E mutation in our cohort of primary skin melanomas and the clinicopathological features of mutated tumors were similar to those reported in the literature, except for the higher proportion of women observed in our group with mutation

Interlaboratory concordance in HER-2 positive breast cancer

Accurate assessment of HER -2 status is essential for identifying patients who will benefit from HER -2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER -2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinoma cases were HER -2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER -2 positive and 12% (17/143) as HER -2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER -2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as those from other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER -2 test results

Među-laboratorijska podudarnost HER-2 pozitivnih karcinoma dojke

Accurate assessment of HER -2 status is essential for identifying patients who will benefit from HER -2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER -2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinoma cases were HER -2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER -2 positive and 12% (17/143) as HER -2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER -2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as those from other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER -2 test results.Ispravna procjena HER -2 statusa je osnova za pronalaženje bolesnika kojima će koristiti HER -2 ciljana terapija. Cilj istraživanja je bio prikazati rezultate podudarnosti između testiranja HER -2 pozitivnih bolesnika oboljelih od raka dojke pri mjesnom i centralnom laboratoriju. U slučajevima nepodudarnih rezultata analize imunohistokemije (IH) i/ili in situ hibridizacije su se izvodile u centralnim laboratorijima. Ukupno 104 od 143 (72,72%) slučaja karcinoma dojke su bili HER -2 pozitivni (biljeg 3+), dok je skoro 14% tumora (20/43) prikazalo nisko (biljeg 2+) i 12% (19/143) negativno imunohistokemijsko bojenje (biljeg 0 i 1+). Nakon ponovljene analize IH i ISH 88% (126/143) se klasificiralo kao HER -2 pozitivni i 12% (17/143) kao HER -2 negativni slučajevi. Dobiveni rezultati su sukladni mnogim istraživanjima koja potvrđuju slične nepodudarnosti pri HER -2 testiranju imunohistokemijom i/ili FISH analizom između mjesnog i centralnog laboratorija. Prema tome, naši rezultati kao i rezultati drugih istraživanja podupiru značenje pravilnog procjenjivanja izvođenja protokola bojenja i dosljednosti interpretacija rezultata HER -2 testiranja

Inter-laboratory comparison of Ki-67 proliferating index detected by visual assessment and automated digital image analysis

Background: Proliferation rate is a major determinant of the biologic behavior of the tumor and provides information that can be used to guide treatment decisions. Methods: This ring study included 27 pathologists from 14 Institutions, in order to assess inter-observer concordance between pathologists in Croatia. We analyzed Ki-67 proliferative index on ten randomly selected breast cancer samples comparing consistency between visual assessment using light microscopy compared to digital image analyses results from one central laboratory as a referral value. Results: When we analyzed Ki-67 as numeric value high concordance rate was found between Ki-67 score visually assessed in all participating Institutions compared to referral value assessed by digital image analysis (ICC 0.76, 95% CI 0.58-0.91), and Krippendorff's alpha was 0.79 (95% CI 0.58-1.00). Concordance was better in slides with higher Ki-67 values. When we categorized Ki-67 values according to generally accepted 20% cut-off value we noticed the lower concordance rate among participants in our study. Conclusion: Proliferation remains one of the most important parameters for tumor characterization helpful in making clinical decisions, but it should be used with great caution. Standardization of the Ki-67 assessment is essential and proliferating index should be expressed as exact numeric value. For patients with proliferative index near the cut-off value, other factors must be considered in making clinical decisions