Clinicopathological significance of the proliferation markers Ki67, RacGAP1, and topoisomerase 2 alpha in breast cancer

WOS: 000382974300005PubMed ID: 27284123Objectives. The aims of this study are to evaluate expressions of Ki67, RacGAP1 (MgcRacGAP) and topoisomerase 2 alpha (TOP2a), the markers related with cell proliferation that have been proposed to affect the prognosis in the literature and correlate the results with clinicopathological parameters of breast cancer patients. Methods. Ki67, RacGAP1, and TOP2a antibodies were applied immunohistochemically to the tissue micrarray blocks of 457 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings (estrogen receptor [ER], progesterone receptor [PR], HER2, cytokeratin [CK]5/6, CK14, epidermal growth factor receptor [EGFR] and vimentin), statistically. Results. Ki67 expression demonstrated direct correlation with TOP2a expression, mitotic count, tumor grade, geographic necrosis, basal-like phenotype. RacGAP1 expression was directly correlated with TOP2a expression, nipple invasion, and number of metastatic lymph nodes, and it was inversely correlated with PR expression. TOP2a expression was directly correlated with vimentin and Ki67 expressions, mitotic count, tumor grade, and geographic necrosis, and nipple invasion, and negatively correlated with ER and PR expressions. Higher TOP2a and Ki67 expressions were correlated with shorter overall survival. Higher TOP2a expression and RacGAP1 positivity were directly correlated with shorter disease-free survival. Conclusion. This study showed that the overexpressions of Ki67, RacGAP1, and TOP2a affect the prognosis adversely, thus to develop target therapies against RacGAP1 and TOP2a as well as using Ki67 as a part of routine pathology practice might be beneficial in breast cancer therapy and prediction of prognosis.Bozok University Scientific Research Projects Unit [2014TF/A92]The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported financially by Bozok University Scientific Research Projects Unit (Project No. 2014TF/A92)

Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer

OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer.MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically.RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025).CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis

GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas

WOS: 000397371700010PubMed ID: 28215639GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p < 0.0001), nuclear grade (p = 0.001), histological grade (p = 0.001), tumor necrosis (p = 0.001), stromal lymphocytic response (p < 0.01), nipple invasion (p = 0.01), metastasis (p = 0.03), vimentin (p = 0.0003), EGFR (p = 0.015) and CK14 (p = 0.001) expressions; and directly associated with ER (p < 0.0001) and progesterone receptor (PR) (p < 0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p < 0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p = 0.001 and p = 0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells

Primary Intracerebral Alveolar Soft Part Sarcoma in an 11-Year-Old Girl: Case Report and Review of the Literature.

Alveolar soft part sarcoma (ASPS), a rarely observed tumor, is a soft tissue sarcoma with an unidentified cell origin. It constitutes 0.5-1.0% of all soft tissue sarcomas. It may appear in various parts of the body, but mostly observed in the trunk and the extremities. It has a high metastasis potential. To the best of our knowledge, only three cases of primary intracranial ASPS without a demonstrable lesion elsewhere is encountered. An 11-year-old girl was operated because of fronto-parietal mass lesion by craniotomy. Pathological examination revealed ASPS and no primary focus was detected. In spite of radiotherapy and chemotherapy as an adjuvant therapy, after 45 months she had a second operation for recurrence of the tumor. Since it is possible to observe metastases in late phases, up to 30 years, the patients must be followed up for a long period. Although radiotherapy and chemotherapy followed by surgery is the most accepted treatment strategy, the prognosis is still poor

A proven case of cutaneous rhizopus infection presenting with severe limb pain very soon after induction treatment in a patient with acute lymphoblastic leukemia.

Objective and Importance. Invasive mucormycosis may complicate the course of patients with hematologic malignancies and has a very high mortality rate. Early diagnosis and aggressive approach combined with surgical and medical treatment have paramount importance for cure. Clinical Presentation. We report here a case of a patient with acute lymphoblastic leukemia presenting with a subcutaneous mass lesion which was sampled by an ultrasound guided needle biopsy. The pathology showed microorganisms with aseptate hyphae with wide, irregular walls and more or less branching with highly vertical angles which suggested a mold infection. The specimen was also cultured where Rhizopus spp. grew. Conclusion. Posaconazole 200 mg QID was commenced. She recovered from neutropenia and pain on day 20 of treatment. After 4 courses of hyper-CVAD chemotherapy, the remaining soft tissue mass was removed surgically and she underwent allogeneic HSCT from a full matched sibling donor under secondary prophylaxis

C-MOPP ve Radyoterapi Alan Hodgkin Lenfomalı Çocuklarda İkincil Neoplaziler: Dört Olgu Sunumu

Patients who survive Hodgkin lymphoma (HL) are at increased risk of secondary neoplasms (SNs). A wide variety of SNs have been reported, including leukemias, non-Hodgkin’s lymphomas, and solid tumors, specifically breast and thyroid cancers. Herein we report subsequent neoplasms in four patients with HL receiving chemoradiotherapy. It is interesting that three SNs, fibrosarcoma, thyroid carcinoma, and retrobulbar meningioma, were observed in the radiation area in one of our patients. A hypopharyngeal epithelioid malignant peripheral nerve sheath tumor as an unusual secondary malignant neoplasm developed in another patient, while a benign thyroid nodule and invasive ductal breast carcinoma were observed at different times in the female patient. Follicular adenoma of the thyroid gland developed in one of our patients.Yaşayan Hodgkin lenfomalı olgularda ikincil neoplazilerin gelişme riski yüksektir. Lösemiler, Hodgkin-dışı malign lenfomalar ve solid tümörler özellikle meme ve tiroid kanserlerini içeren çok çeşitli ikincil malign neoplaziler raporlanmıştır. Burada kemoradyoterapi alan Hodgkin lenfomalı dört olguda gelişen ikincil neoplaziler sunulmuştur. İlginç olarak hastalarımızdan birinde ışın alanında üç ikincil neoplazm; fibrosarkom, tiroid karsinom ve retrobulber meningiom, diğer bir hastamızda sıradışı ikincil malign neoplazm olarak hipofaringeal epitelyal malign periferik sinir kılıfı tümörü gelişirken kız hastada farklı zamanlarda benign tiroid nodülü ve invaziv duktal meme kanseri saptandı. Bir hastamızda ise, tiroidde folliküler adenoma gelişti