ABSTRACT
AIM: The aim of this study was to validate the role of fluorescence in situ hybridization (FISH) in investigating HER2/neu gene amplification (human epidermal growth factor receptor 2) in patients with HER2/neu equivocal breast cancer diagnosed on immunohistochemistry (IHC). MATERIALS AND METHODS: This was a retrospective study conducted from January 2013 to October 2017. A total of 134 patients diagnosed with invasive breast carcinoma and HER2/neu equivocal status on IHC were analyzed. Also, the cases for the years 2016 and 2017 formed a subgroup that was analyzed further to study the impact of pre-analytical factors on IHC and FISH results. RESULTS: A total of 134 women with HER2/neu IHC equivocal breast cancer were included in the study with a median age of 50 years (range 25–81). HER2/neu amplification by FISH was noted in 72 (54%) cases, whereas it was non-amplified in 52 (39%) cases. Ten cases were reported as equivocal even on FISH (ASCO/CAP 2013 guidelines). Polysomy 17 was noted in 55 cases (41%), of which 26 patients were≤50 years and 29 patients were >50 years of age. Twenty (36%) of these 55 cases showed HER2/neu amplification, whereas 26 (48%) cases were non-amplified and 9 (16%) cases were reported as equivocal on FISH. Also, more than half of the polysomy cases were hormone receptor negative. CONCLUSION: IHC is a good screening tool for negative and positive results. Any patient targeted for trastuzumab therapy should undergo confirmation of HER2/neu equivocal status by FISH analysis. We also suggest that if a non-classical FISH pattern is seen, the test should be repeated with a non-centromeric chromosome 17 reference locus probe for better treatment planning.
ABSTRACT
Objective: To evaluate the cytogenetics abnormalities in pediatric ALL cases and to correlate the cytogenetics Philadelphia chromosome - positive with the Fluorescence In - Situ Hybridization results. Methods: Retrospective cytogenetics and FISH analysis of the Bone marrow samples of both adult and pediatric patientswere done. However, since the inclusion criteria for this study was pediatric ALL, only the data of the pediatric patients were taken for this study. For the prospective samples, the cytogenetic analyses and Fluorescence in - Situ Hybridization were performed on the procured samples. The cytogenetics and FISH test were performed as per the standard protocol of our lab and were analysed as per the standard guideline. The cytogenetics Philadelphia chromosome - positive were correlated with the Fluorescence In - Situ Hybridization results and vice versa. Results: In our study of 50 pediatric ALLB patients, two patients showed low Ph+ by FISH. A confirmatory test by conventional cytogenetics revealed a rare association of Philadelphia chromosome positive along with the cytogenetics abnormality involving the MLL gene as well. One of the patient showed a karyotype of 46,XY,del(9) (p21),t((10;11)(p12;q21)[7]/46,XY,del(9)(p21)[9]/46,XYdel(22)(q11.2)[3] and the other patient showed 46, XX, t(9;11) (p13;q23)),?del(22)(q11.2)[6]/46,XX,del (11) (q23) [8]/46, XX[5] which were confirmed by cytogenetics and Fluorescence In - Situ Hybridization (FISH). Two patients showed complete Ph+ve and one patient showed normal karyotype along with tetraploidy. The rest of the cases showed either a normal karyotype or an insignificant abnormality. Conclusion: In our study of 50 pediatric ALL patients, two cases showed a rare association of Philadelphia chromosome positive along with a cytogenetics abnormality involving the MLL gene. Apart from the rare findings in our study, emphases is also made on the confirmatory test by cytogenetics incidence of low Ph+ve by FISH and vice versa and a need for larger collaborative studies and intense follow up of the treatment and the prognosis of this subset of patients to determine the prognostic pattern to improve the treatment options for these kind of rare patients.
ABSTRACT
BACKGROUND: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a Tertiary Care Center in South India. MATERIALS AND METHODS: This retrospective descriptive study includes 51 cases of ES in children aged below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic, primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ hybridization (FISH). RESULTS: Fifty‑three percent were female and 47% were male with mean age of 10 years. The most common site of involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow‑up in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%). All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical histomorphology. CONCLUSION: ESFT had wide histological variation which required confirmation by ancillary studies.