Janusz Ryś

Survival of breast cancer patients according to changes in expression of selected markers between primary tumor and lymph node metastases

BACKGROUND The differences between primary and metastatic tumor cells might be important for treatment selection and prognostication. MATERIALS & METHODS Expression of ER, PR, HER2, CK5/6, EGFR, Ki-67, Ep-CAM, P-cadherin, CD24, CD44, ALDH was assessed immunohistochemically in primary tumor (T) and corresponding synchronous nodal metastases (LNM) in 156 invasive ductal breast cancer patients (T ≥1, N ≥1, M0). RESULTS Independent negative prognostic factors for disease-free survival were pN3, ALDH immunopositivity in LNM, nonluminal A subtype in LNM, reduction of Ep-CAM expression in LNM, lack of changes or enhancement of CK5/6 and ALDH expression in LNM. DISCUSSION Our results suggest that in some cases expression of markers in lymph node metastases might bring additional prognostic information to that obtained from primary tumor.

Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting

Aim: Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors. Material and methods: Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry. Results: Lower Ki-67LI was observed in EGFR-immunonegative and in PTEN-immunopositive tumours. MUC4-immunonegative tumours more frequently were PTEN- and HER3-immunonegative. Favourable metastasis-free survival was observed in patients with tumours characterized by Ki-67LI≤50% (p=0.027), HER3 immunonegativity or PTEN immunopositivity (vs. tumours with HER3 expression and lack of PTEN expression, p=0.043), additionally, the trend was observed for patients with pN0+pN1 pathological tumour stage (vs. pN2+pN3) (p=0.086). Cox model revealed that independent negative prognostic factors were: (i) Ki-67LI>50% (p=0.014, RR=4.6, 95% CI 1.4-15.4), (ii) HER3 immunopositivity together with PTEN immunonegativity (p=0.034, RR=3.7, 95% CI 1.1-12.5). Conclusion: The results of our study suggest that combined analysis of HER3 and PTEN expression might bring information on trastuzumab sensitivity in the group of HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.

Metaplastic breast cancer with rapidly progressive recurrence in a young woman: case report and review of the literature

Corresponding author: Jerzy W. Mituś MD, PhD Department of Surgical Oncology Centre of Oncology Maria Skłodowska-Curie Memorial Institute Krakow Branch 11 Garncarska St 31-115 Krakow, Poland Phone: +48 12 422 49 28 Fax: +48 12 423 10 76 E-mail: jerzy.mitus@gmail.com 1 Department of Surgical Oncology, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Krakow, Poland 2 Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland 3 Clinic of Oncology, Department of Breast and Chest Cancer, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Krakow, Poland 4 Department of Tumour Pathology, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Krakow, Poland 5 Department of Systemic and Generalized Malignancies, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Krakow, Poland

Relationship between HER2 gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment

Background The aim of the study was to investigate if parameters associated with human epidermal growth factor receptor type 2 (HER2) status (HER2 gene copy number, HER2/CEP17 ratio or polysomy of chromosome 17) are related to various biological features potentially responsible for trastuzumab resistance (PTEN, IGF-1R, MUC4, EGFR, HER3, HER4, and mutation status of PIK3CA) as well as their influence on survival of HER2-positive breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Patients and methods The investigated group consisted of 117 patients with invasive ductal breast cancer (T≥1, N≥0, M0) with overexpression of HER2, who underwent radical surgery between 2007 and 2014. Status of ER, PR, and HER2 expression was retrieved from patients’ files. HER2 gene copy number was investigated by fluorescence in situ hybridization using PathVysion HER-2 DNA Probe Kit II. Expression of PTEN, IGF-1R, MUC4, EGFR, HER3, and HER4 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. PIK3C mutation status was determined by qPCR analysis. Results Overexpression of HER2 protein (IHC 3+) and ER negativity corresponded to higher HER22 copy number and HER2/CEP17 ratio (.<0.001). Tumors with polysomy were characterized by higher HER22 gene copy number but lower HER2/CEP17p ratio (p<0.026, p<0.001). Patients with tumors featuring HER3 immunonegativity or low HER2/CEP17 ratio (#4) were characterized by 100% metastasis-free survival (.=0.018, p=0.062). Conclusion Presence of both unfavorable factors, ie, HER3 expression and high HER2/CEP17 ratio, allowed to distinguish a group of patients with worse prognosis (.=0.001).

The role of histology, grading, location of tumour and ploidy in evaluation of outcome in patients with liposarcoma

Department of Tumour Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Kraków, Poland The review of literature indicates that several clinico-morphological factors such as location of the primary tumour as well as its size, histologic subtype, and grade or even selected molecular changes may significantly affect survival of liposarcoma (LPS) patients. Data concerning prognostic importance of DNA ploidy status in LPS cells are extremely limited and results of flow cytometry (FCM) studies have never been compiled with the current classification of malignant adipocytic tumours. Based on evaluation of material from 54 liposarcomas which was available for both histological and FCM analysis, we distinguished four prognostic groups of patients. The best prognosis was noticed for diploid and grade G1 well-differentiated or myxoid liposarcomas localised on extremities. None of the patients with lipoma-like WDLPS and myxoid liposarcoma grade 1 metastasised, while metastases were observed among patients with dedifferentiated LPS (70% of 5-year MFS) and cellular myxoid or round cell liposarcoma (20% of 5-year MFS, only). The metastasis-free survival curves for the above mentioned groups of patients differed significantly (p = 0.00001).

Selected abbreviations and new terms in breast pathology — a guide for clinicians

The aim of this article is to present briefly new pathological entities which are recently increasingly commonly used in pathology reports, as well as to discuss their clinical consequences. The new WHO classification of breast diseases includes, inter alia , invasive carcinoma of no special type: this is not a specific entity, but rather a group of malignancies without specific features. The lobular hyperplasia group includes a classical variant and a pleomorphic variant of lobular carcinoma in situ, as well as atypical lobular hyperplasia. The ductal hyperplasia group, according to the current revision of the WHO classification of breast diseases, encompasses: typical (i.e. non-atypical) ductal hyperplasia, columnar cell change, columnar cell hyperplasia, atypical ductal hyperplasia. The mesenchymal breast hyperplasia group includes pseudoangiomatous stromal hyperplasia. We briefly discuss the above mentioned entities together with their respective clinical and therapeutic consequences.

Pathology of Differentiated Thyroid Cancers

This chapter discusses briefly the pathological aspects of differentiated thyroid cancers. The authors explain the histological features of thyroid cancers and possible approaches for making a firm diagnosis. The prognosis of different subtypes of differentiated thyroid cancer is also discussed.