High Intraepithelial Mast Cell Density in Warthin's Tumor.

BACKGROUND/AIM: Warthin's tumor, the second most frequent neoplasia of the parotid gland, is characterized by a proliferation of both epithelial and lymphoid components. In addition to epithelial and lymphoid cells, various other cell types are implicated to varying degrees in the immune response. Notably, mast cells have long been recognized as a consistent cell population within this tumor. Despite the historical acknowledgment of mast cell presence, their true distribution and significance within Warthin's tumor remain unclear. In this study, we aimed to elucidate the distribution and significance of mast cells in Warthin's tumor. MATERIALS AND METHODS: Histochemical and immunohistochemical methods were employed for the evaluation of mast cells within tumor specimens. RESULTS: Our study revealed a notable concentration of mast cells in the epithelial component of Warthin's tumor. Microscopic examination showed predominant lymphoid and epithelial elements with occasional cystic formations. Immunohistochemical analysis identified mast cells in both components, emphasizing their role in the tumor microenvironment. Double immunostaining (mast cell tryptase and CD34) revealed no significant correlation between mast cells and blood vessels. Intraepithelial mast cells (IEMCs) had a significantly higher density in the epithelial component, suggesting a potential association with the tumor's benign nature. The relationship between IEMCs and epithelial cells, especially in the presence of cystic structures, offers valuable insights into the unique features of Warthin's tumor. CONCLUSION: Our study contributes to the understanding of mast cells in Warthin's tumor, highlighting a substantial concentration within the epithelial component. This knowledge may pave the way for further investigations into the roles of mast cells in the pathogenesis and treatment of Warthin's tumor.

Plurihormonal Pituitary Neuroendocrine Tumors: Clinical Relevance of Immunohistochemical Analysis.

Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth hormone (GH) and prolactin (PRL), but other unusual combinations have been reported, such as GH and ACTH. Usually, the clinical dominance in these cases is related to GH hypersecretion. In these cases, immunohistochemistry (IHC) of transcription factors (TFs) is very useful for an accurate diagnosis. We included 42 patients diagnosed with pituitary neuroendocrine tumors (PitNETs): 37 patients with a confirmed diagnosis of acromegaly, and 5 patients with prolactinomas. All patients underwent transsphenoidal surgical intervention. We correlated the immunohistochemical features of plurihormonal PitNETs with clinical, hormonal, and imaging data. Tumor specimens were histologically and immunohistochemically examined. Based on the 2022 WHO classification, using IHC, 13 patients exhibited positive staining for more than one hormone, while unusual combinations like GH + ACTH and PRL + ACTH were also identified in other cases. Unusual cell combinations that produce hormones unrelated histogenetically, biochemically, or through regulatory mechanisms can appear and may display aggressive behavior, persistent disease, and high recurrence. We have not identified a clear correlation with the prognosis of these rare PitNETs.

Mast Cell: A Mysterious Character in Skin Cancer.

Cutaneous malignancies represent a real concern and burden for the healthcare system, not only due to their increased frequency, but also due to the significant number of deaths attributed to these types of cancer. The genesis of tumors, their progression and metastasis are highly complex and researched subjects; apparently, mast cells (MCs) constitute an important piece in the complicated jigsaw puzzle of cancer. This article reviews the current knowledge of the roles MCs might play in the development of cutaneous malignancies. Besides their well-known and studied role in allergic reactions, MCs are linked to multiple and various disorders, including cancer. MCs exhibit incredible heterogeneity, being able to secrete numerous mediators that influence the tumor microenvironment and tumor cells. They are involved in many physiological and pathological processes, such as inflammation and angiogenesis. In this context, it is paramount to explore the advancements made so far in elucidating the roles that MCs have in skin cancer because they might provide valuable therapeutic targets in the future. Controversial and conflicting results were obtained across the studies examined.

The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research.

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives.

The Follicular Dendritic Cells and HPV 18 Interrelation in Head and Neck Squamous Cell Carcinomas of the Larynx.

Background and Objectives: Even if they are cells of controversial origin (mesenchymal, perivascular, or fibroblastic), follicular dendritic cells (FDC) are present in all organs. The aim of this study was to establish the FDC expression pattern and its interrelation with HPV 18 expression in laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Fifty-six cases of LSCC were evaluated by simple and double immunostaining. The following score was used: 0 (negative or few positive cells), 1 (10-30% of positive cells), 2 (30-50% of cells), and 3 (over 50% of cells). Results: The expression of CD 21-positive cells with dendritic morphology (CDM) was noticed in the intratumoral area of conventional (well and poorly differentiated types and HPV 18 positive cases with a value of 2 for the score) and papillary types (HPV-18 negative cases with a score of 1). The highest value of 2 for the score of CDM in HPV-18 positive cases was found in the peritumoral area of well- and poorly-differentiated conventional LSCCs. A significant correlation was found between scores of CDM from the intratumoral area and those of the peritumoral area (p = 0.001), between CDM and non-dendritic morphology cells (NDM) of the intratumoral area (p = 0.001), and between HPV-18 status and peritumoral NDM cells (p = 0.044). Conclusions: The FDC and NDM cell score values of intratumoral and peritumoral areas may represent important parameters of LSCCs. This may contribute to a better stratification of laryngeal carcinoma cases and the individualized selection of clinical treatment protocols.

Novel Expression of Thymine Dimers in Renal Cell Carcinoma, Demonstrated through Immunohistochemistry.

Despite significant developments in renal cell carcinoma (RCC) detection and molecular pathology, mortality has been steadily rising. Advanced RCC remains an incurable disease. Better clinical management tools, i.e., RCC biomarkers, have yet to emerge. Thymine-dimers (TDs) were traditionally considered photo-dependent pre-mutagenic lesions, occurring exclusively during ultra-violet light exposure. Non-oxidative, direct, and preferential byproducts of DNA photochemical reactions, TDs, have recently shown evidence regarding UVR-independent formation. In this study, we investigate, for the first time, TD expression within RCC tumor tissue and tumor-adjacent healthy renal parenchyma using a TD-targeted IHC monoclonal antibody, clone KTM53. Remarkably, out of the 54 RCCs evaluated, 77.8% showed nuclear TD-expression in RCC tumor tissue and 37% in the tumor-adjacent healthy renal parenchyma. A comprehensive report regarding quantitative/qualitative TD-targeted immunostaining was elaborated. Two main distribution models for TD expression within RCC tumor tissue were identified. Statistical analysis showed significant yet moderate correlations regarding TD-positivity in RCC tissue/tumor-adjacent healthy renal parenchyma and TNM stage at diagnosis/lymphatic dissemination, respectively, indicating possible prognostic relevance. We review possible explanations for UVR-independent TD formation and molecular implications regarding RCC carcinogenesis. Further rigorous molecular analysis is required in order to fully comprehend/validate the biological significance of this newly documented TD expression in RCC.

Podoplanin and PROX1 Expression in Hypercaloric Diet-induced Pancreatic Injuries.

BACKGROUND: The role of podoplanin (PDPN) and homebox prospero gene 1 (PROX1) in early stages of pancreatic islet changes induced by hypercaloric diet is unclear. The aim of this study was to study PDPN and PROX1 variability in pancreatic islets after a hypercaloric diet in a rat experimental model. MATERIALS AND METHODS: Pancreatic biopsies harvested from Sprague-Dawley rats at 3, 6, and 9 weeks following hypercaloric diet intake were evaluated for morphological and molecular changes of Langerhans islets based on PDPN and PROX1 expression Results: Six weeks of hypercaloric diet induced hypertrophy of pancreatic islets with focal expression of Pdpn and Prox1 mRNA. At 9 weeks of hypercaloric diet, strong peri-insular inflammation was found around hypertrophic islets highly expressing PDPN, and lacking Prox1 mRNA and protein expression. CONCLUSION: This is the first report of Pdpn and Prox1 mRNA expression variability and involvement in early steps of pancreatic islet changes following hypercaloric food intake.

Intracellular Chloride Ion Channel Protein-1 Expression in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Chloride intracellular channel 1 (CLIC1) represents a promising target for personalized therapy. Our aim was to assess CLIC1 expression in clear cell renal cell carcinoma (cc RCC) and identify its possible prognostic role. MATERIALS AND METHODS: Fifty cases of cc RCC were evaluated and selected for immunohistochemistry. CLIC1 expression was correlated with tumor grade, invasion and heterogeneity. RESULTS: A total of 87.5% of the cases were CLIC1 positive, with either a homogeneous (31.42%) or a heterogeneous (68.57%) pattern. Low, mild and strong CLIC1 expressing tumors were defined based on nuclear (N), cytoplasmic (C), membrane (M) or combinations of them (NC, NM, CM, NCM) in terms of CLIC1 distribution. A significant correlation was found between tumor grade and percent of positive tumor cells (p=0.017). For G3 tumors, CLIC1 cytoplasmic expression was strongly correlated with high expression status (p=0.025) and tumor heterogeneity (p=0.004). CLIC1 expression was also correlated with metastasis (p=0.046). CONCLUSION: We defined four cc RCC groups depending on G, CLIC1 expression and pattern: i) G3/NM/low CLIC1+, ii) G2/CM/mild CLIC1+ iii) G1 or G2/NM or CM /high CLIC1+, and iv) G2/M /high CLIC1.

Mast Cells as an Indicator and Prognostic Marker in Molecular Subtypes of Breast Cancer.

BACKGROUND/AIM: Mast cells (MCs) represent the most controversial non-malignant element of the tumor microenvironment. Our aim was to study how MCs density and distribution (intratumoral-MCit versus peritumoral-MCpt) relate to tumor grade and molecular subtypes. MATERIALS AND METHODS: MCs tryptase immunohistochemistry was performed on 80 cases of breast carcinomas. RESULTS: For Luminal A tumors, a partial correlation was detected between MCit and progesterone receptor (PR) (p=0.005). Luminal B tumors showed a significant correlation between MCpt and age (p=0.009), estrogen receptor (ER) (p=0.017) and PR (p=0.035). MCit and MCpt were strongly interrelated in this subtype (p=0.002) and in triple-negative breast cancers (p=0.002). In HER2 subtype, MCpt tumors were significantly correlated with HER2 (p=0.044). In G2 tumors, MCpt correlated with ER (p=0.015) and PR (p=0.038) while in G3 tumors ER correlated with both MCit (p=0.009) and MCpt (p=0.000487) tumors. CONCLUSION: MCs dynamics are strongly influenced by hormone receptors and HER2 status. MCit increased in aggressive tumor types and is a worse prognostic factor.

Evaluation of Podoplanin Expression in Hepatocellular Carcinoma Using RNAscope and Immunohistochemistry - A Preliminary Report.

BACKGROUND: Podoplanin (PDPN), a mucin-type transmembrane glycoprotein, is expressed in a variety of human cancer types, and contributes to tumor progression. Our goal was to evaluate PDPN expression in hepatocellular carcinoma (HCC) using both immunohistochemistry (IHC) and RNAscope in situ hybridization. MATERIALS AND METHODS: Twenty patients with HCC who underwent partial hepatectomy with curative intent were retrospectively analyzed. RESULTS: IHC gave positive results in 11 cases, while RNAscope assay for PDPN detected amplification in 16 cases. A significant association was noted between PDPN protein expression and histological tumor grade (p=0.036). Four cases that had negative PDPN results by RNAscope were also negative by IHC, while the remaining five cases with negative results by IHC were positive by RNAscope. A positive relationship was found between PDPN mRNA protein expression (p<0.001). CONCLUSION: Our preliminary results suggest that PDPN contributes to the malignant potential of HCC. RNAscope proved to be a more sensitive and reliable method than IHC in PDPN detection.

Mast Cells: Key Players in the Shadow in Oral Inflammation and in Squamous Cell Carcinoma of the Oral Cavity.

Although mast cells (MCs) have been discovered over 130 years ago, their function was almost exclusively linked to allergic affections. At the time being, it is well known that MCs possess a great variety of roles, in both physiologic and pathologic conditions. In the oral tissues, MCs release different proinflammatory cytokines, tumor necrosis factor alpha (TNF-α), that promote leukocyte infiltration in various inflammatory states of the oral cavity. These cells play a key role in the inflammatory process and, as a consequence, their number changes in different pathologic conditions of the oral cavity, like gingivitis, periodontitis, and so on. MCs also represent a rich source of proteases, especially of mast cell tryptase and chymase, which directly degrade the extracellular matrix through their proteolytic activity and thus indirectly stimulate angiogenesis and facilitate invasion and metastasis. It may be stated that mast cells could have an impact on primary tumor development, progression, and metastases in oral squamous cell carcinoma. By understanding the role of mast cells in the pathogenesis of different inflammatory and tumor diseases of the oral cavity, these cells may become therapeutic targets that could possibly improve the prognosis and survival of these patients.

Monoamine oxidase inhibition improves vascular function in mammary arteries from nondiabetic and diabetic patients with coronary heart disease.

Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived H2O2 contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with and without diabetes mellitus subjected to coronary artery bypass grafting. To this aim, the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments. Clorgyline (irreversible MAO-A inhibitor), selegiline (irreversible MAO-B inhibitor), and moclobemide (reversible MAO-A inhibitor) were applied in the organ bath (10 µmol/L). MAO expression was assessed by immunohistochemistry. We found a constant impairment of EDR that has been significantly attenuated in the presence of the MAO-A and MAO-B inhibitors in both groups of coronary heart disease patients. MAO-B was the dominant isoform in all human diseased vessels. In conclusion, in vitro inhibition of MAO significantly improved EDR in human mammary arteries, regardless of the presence of diabetes. These data suggest that MAO inhibitors might be useful in restoring endothelial response in clinical conditions associated with increased oxidative stress, such as coronary artery disease and diabetes.

The Involvement of PDGF-B/PDGFRß Axis in the Resistance to Antiangiogenic and Antivascular Therapy in Renal Cancer.

BACKGROUND/AIM: Studies developed in the field of platelet-derived growth factors/platelet-derived growth factor receptors (PDGFs/PDGFRs) inhibition have focused on the therapeutic effects on tumor cells, neglecting their potential effects on tumor blood vessels. We herein propose a differential and critic assessment of platelet-derived growth factor B (PDGF-B) and platelet-derived growth factor receptor ß (PDGFRß) in renal cell carcinoma, correlated with the four main vascular patterns previously reported by our team. MATERIALS AND METHODS: PDGF-B and PDGFRß were evaluated on 50 archival paraffin embedded specimens related to vascular endothelial growth factor (VEGF), its inhibitory isoform VEGF165b and vascular patterns. RESULTS AND CONCLUSION: Our results support the involvement of VEGF165b in the phosphorylation of PDGFRß with an inhibitory effect on endothelial proliferation and migration. The simultaneous action of PDGF-B/PDGFRß and VEGF165b on the same type of receptor may explain the resistance to antiangiogenic therapy, which depends on the degree of modulation of PDGFRß phosphorylation.

Healing Potential of the Anterior Cruciate Ligament Remnant Stump.

AIM: The aim of this study was to analyze the microstructural architecture and cellular differentiation of the anterior cruciate ligament (ACL) stumps in different stages after injury, as this could augment graft biointegration. MATERIALS AND METHODS: The histological appearance and immunoreaction for cluster of differentiation 34 antigen (CD34) of 54 biopsies from 27 remnants were compared to 10 biopsies from 5 normal cruciate ligaments. RESULTS: CD34 reaction in endothelial cells, fibroblasts and fibrocytes was consistently positive in small synovial vessels. Remnants also exhibited CD34(+) cells among collagen fibers. Blood vessel density varied between specimens. The mean vascular microdensity was 43 per ×200 field in remnants compared to 15.2 in controls. A total of 94.44% of remnant ACL samples had significant hyperplasia of stellate and fusiform stromal cells, CD34(+); 22.4% had developed capillary vessels inside the ligament; 33% exhibited ongoing angiogenesis. CONCLUSION: Significant differences exist between torn and intact ACL regarding microvascularization. The remnants contain stellate stromal cells and CD34(+) fibrocytes, and display angiogenesis both at synovia as well as in the ligament itself. These findings underline the potential contribution to neoligament healing when remnants are preserved.

Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery.

Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.

Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies.

AIM: Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid. MATERIALS AND METHODS: We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types. RESULTS: Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we observed a predominance of immature and intermediate blood vessels compared to mature ones. A significant correlation was found between immature tumor blood vessels and tissue prolactin expression, as assessed by immunhistochemistry (p=0.044). A partial correlation was found between serum (p=0.036) and cerebrospinal prolactin values (p=0.006) with immature and intermediate blood vessels. Also, a partial correlation has been reported only between mature blood vessels and cerebrospinal fluid prolactin values (p=0.008). No correlation was obtained for other types of pituitary adenomas. CONCLUSION: Our results suggest a strong involvement of prolactin with a dual role in pituitary adenomas vasculature remodelling by acting both on endothelial and perivascular cells, a finding that could partially explain discrepancies between clinical diagnosis and hormonal profile.

Crosstalk between EGFR and p53 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. MATERIALS AND METHODS: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. RESULTS: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). CONCLUSIONS: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

Lymphangiogenesis as a prerequisite in the pathogenesis of lung fibrosis.

Despite increasing knowledge on the cellular and molecular mechanisms involved in pulmonary fibrosis, its therapeutic options are still limited. The study of lymphangiogenesis has contributed to a better understanding of tumor growth and metastasis, with a major impact upon changes in therapeutic strategies and this was followed by the research of lymphatic vessels in other pathological conditions. Some data support the possible role of lymphangiogenesis in the pathogenesis of lung fibrosis. However, at the time of diagnosis for each patient with a fibrotic interstitial lung disease, it is necessary to predict the prognosis and to choose for individual targeted-therapy. Our aim was the characterization of lymphangiogenesis as a useful tool to stratify patients with lung fibrosis. We evaluated the presence, morphology and density of D2-40-positive lymphatic vessels and co-localization of D2-40/Ki67 in pulmonary fibrosis with different degrees of severity and without a specific etiology. Lymphatic vessel density did not correlate with severity grade and ranged between 4.66 to 38.33 vessels/×40 field, with the highest value in degree III of fibrosis. An intense proliferative activity of lymphatic endothelial cells was found in 24% (6 out of 25) of cases. The morphology of lymphatics and the presence of splitting combined with the proliferative activity of endothelial cell pillars suggested two different mechanisms in the formation new lymphatic vessels. Our results support the hypothesis that the activity and ongoing evolution of fibrosis can be predicted through the characterization of lymphangiogenesis but its presence or absence cannot predict the severity of fibrosis.

Endothelial progenitor cells contribute to the development of ovarian carcinoma tumor blood vessels.

Only a few studies in the literature have reported the contribution of endothelial progenitor cells (EPCs) in ovarian tumors, and with regard to malignant tumors, the data on the pre-existing endothelium insertion rate and the extent to which these cells contribute to tumor angiogenesis is controversial. The present study demonstrated the existence of EPCs and evaluated the expression of two markers, AC133 (also known as cluster of differentiation 133 or prominin) and tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2), signaling the presence of EPCs in the pre-existing endothelium. In total, 62 female patients who were diagnosed with ovarian tumors were retrospectively selected over a four-year period. Immunohistochemical analyses used Tie2 and AC133 as primary antibodies. In total, 27.4% of ovarian tumor cases expressed AC133 and Tie2 in blood vessel endothelial cells. The expression of these two markers did not correlate with the clinicopathological prognostic parameters, histological type, vascular microdensity or vessel type. The expression of AC133 and Tie2 in blood vessel endothelial cells contributes to angiogenesis progression in cases where the budding process is reduced or absent, as shown by the inverse correlation with the rate of proliferation of the endothelial cells.

Hormone receptors and HER2 expression in primary breast carcinoma and corresponding lymph node metastasis: do we need both?

BACKGROUND: Scattered studies report on controversial results concerning evaluation of primary breast tumors and their matched lymph node metastases. Aim. To investigate the molecular profile of primary breast tumors and corresponding lymph node metastases (LNM) based on estrogen receptor (ER), progesterone receptor (PR) and human epiderma growth factor receptor-2 (HER2 protein). MATERIALS AND METHODS: Sixty-six primary tumors and corresponding axillary lymph node metastases were evaluated by immunohistochemistry for ER, PR and HER2 protein. According to these markers, cases were stratified as Luminal A, B, HER2 subtypes and triple-negative. Results. Thirteen out of 66 cases (19.7%) exhibited different tumor cell phenotypes in nodal metastases compared to primary breast tumors. All cases with hybrid phenotype had metastases with a pure HER2 phenotype. The most frequent switching was observed from luminal A to luminal B phenotype. CONCLUSION: The high rate of discrepancy between primary tumor and nodal metastasis phenotype imposes the need for a comparative assessment of both primary tumor and nodal metastasis before any therapeutic decision, in order to avoid recurrence and to improve patient prognosis and overall survival.