The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations.

Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade (p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level (p = 0.002), and with ki-67 (p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter (p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.

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.

Proliferating Lymphatic Endothelial Cells as a Prognostic Marker in Head and Neck Squamous Cell Carcinoma.

Podoplanin and Ki-67 are two important markers of cancer progression. The aim of this study is to evaluate double immunostaining for Ki-67 and podoplanin in head and neck squamous cell carcinoma (HNSCC), and to observe the involvement of lymphagiogenesis in tumoral and peritumoral areas, as well as the density of tumor proliferation correlated with histopathological grading. A total of 50 patients with HNSCC were included in this study. We carried out a morphological evaluation of tissue samples, after that, cases were selected for double Ki-67 and podoplanin immunostaining. Podoplanin expression was significantly correlated with histopathological grade (p < 0.05; p = 0.037) and expression of Ki-67 (p < 0.05; p = 0.050). A high expression of podoplanin, as well as of the proliferation factor Ki-67, was observed in histopathological grade G3 and the correlation between these (p < 0.05; p = 0.028), and implication of LMVD and LVI was not significant (LMVD p = 0.577; LVI p = 0.976). This study demonstrated the importance of double immunolabeling in assessing lymphagiogenesis and tumor proliferation in correlation with histopathological grades in HNSCC.

Correlations on Phenolic Screening Related to In Vitro and In Ovo Assessment of Ocimum basilicum L. Hydro-Alcoholic Extracts Used as Skin Active Ingredient.

The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves' extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.

Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth.

Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Is Circular Fibrin Sealing of Low Rectal Anastomosis Able to Prevent Leakage in 21-Day Follow-up? Randomized Experimental Trial in Pigs.

Purpose. Clinically apparent anastomotic leakage (AL) after low anterior rectal resection (LAR; <7 cm from anal verge) using circular double-stapled anastomosis without defunctioning stoma is up to 37.5%. However, it is unclear whether there is reduction of LAR after 21 postoperative days without defunctioning stoma but with extraluminal anastomotic application of fibrin sealant. Methods. Forty-eight-week-old pigs underwent LAR and circular double-stapled anastomosis in end-to-end technique (descendo-rectostomy). Animals were randomized into therapy and control group (cg). Therapy group (n = 20) received additional extraluminal circular anastomotic application of fibrin sealant. Objective was to assess incidence of clinically apparent and nonclinically apparent leakage through the 21st postoperative day. Remaining animals were sacrificed on the 21st day, and anastomotic region was analyzed. In case of earlier diagnosed AL, animals were sacrificed. Results. In cg, we observed clinically and nonclinically AL in 20% (n = 4). No animal was identified with a nonclinical-apparent leakage in this group, and all 4 animals with leakages presented clinical signs. In the therapy group, no animal (0/20) developed clinically apparent leakage signs. There were no leakages in this group, but 3 animals had ulcerative lesions without leak and without clinical signs. These lesions were observed intraluminally at crossing of staple lines after 21 days. In one of these animals, incomplete leakage was observed, blocked by fibrin sealant. Conclusion. In circular stapled colorectal anastomosis, circular fibrin glue sealant successfully protected anastomotic intraluminal wall defects at crossing of staple lines, reducing leakage rate from 20% to 0% (cg vs therapy group) after 21 postoperative days.

Hyaluronic Acid/Bone Substitute Complex Implanted on Chick Embryo Chorioallantoic Membrane Induces Osteoblastic Differentiation and Angiogenesis, but not Inflammation.

Microscopic and molecular events related to alveolar ridge augmentation are less known because of the lack of experimental models and limited molecular markers used to evaluate this process. We propose here the chick embryo chorioallantoic membrane (CAM) as an in vivo model to study the interaction between CAM and bone substitutes (B) combined with hyaluronic acid (BH), saline solution (BHS and BS, respectively), or both, aiming to point out the microscopic and molecular events assessed by Runt-related transcription factor 2 (RUNX 2), osteonectin (SPARC), and Bone Morphogenic Protein 4 (BMP4). The BH complex induced osteoprogenitor and osteoblastic differentiation of CAM mesenchymal cells, certified by the RUNX2 +, BMP4 +, and SPARC + phenotypes capable of bone matrix synthesis and mineralization. A strong angiogenic response without inflammation was detected on microscopic specimens of the BH combination compared with an inflammatory induced angiogenesis for the BS and BHS combinations. A multilayered organization of the BH complex grafted on CAM was detected with a differential expression of RUNX2, BMP4, and SPARC. The BH complex induced CAM mesenchymal cells differentiation through osteoblastic lineage with a sustained angiogenic response not related with inflammation. Thus, bone granules resuspended in hyaluronic acid seem to be the best combination for a proper non-inflammatory response in alveolar ridge augmentation. The CAM model allows us to assess the early events of the bone substitutes⁻mesenchymal cells interaction related to osteoblastic differentiation, an important step in alveolar ridge augmentation.

Predictive Models for Fast and Effective Profiling of Kinase Inhibitors.

In this study we developed two-dimensional pharmacophore-based random forest models for the effective profiling of kinase inhibitors. One hundred seven prediction models were developed to address distinct kinases spanning over all kinase groups. Rigorous external validation demonstrates excellent virtual screening and classification potential of the predictors and, more importantly, the capacity to prioritize novel chemical scaffolds in large chemical libraries. The models built upon more diverse and more potent compounds tend to exert the highest predictive power. The analysis of ColBioS-FlavRC (Collection of Bioselective Flavonoids and Related Compounds) highlighted several potentially promiscuous derivatives with undesirable selectivity against kinases. The prediction models can be downloaded from www.chembioinf.ro .

Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?

In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.

VEGF mRNA assessment in human pterygium: a new 'scope' for a future hope.

PURPOSE: The lack of powerful evidence to support the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in human pterygium can be attributed to incomplete VEGF expression assessment by restrictive use of immunohistochemistry only and failure to use the molecular methods able to confirm immunohistochemical findings. By adding at least one more sensitive method to assess human pterygium VEGF expression, a more accurate selection of patients for bevacizumab therapy could be done and this would improve the efficacy of anti-VEGF therapy in human pterygium. METHODS: We assessed VEGF mRNA amplification on paraffin-embedded specimens by applying the RNAscope method for the first time in human pterygium, an in situ hybridization-based technique able to detect VEGF mRNA as a single gene copy on paraffin-embedded samples. RESULTS: Heterogeneous VEGF mRNA distribution and amplification inside the epithelial compartment of human pterygium were observed. Despite previous reports concerning the immunohistochemical expression of VEGF in the human pterygium fibrovascular compartment, no stromal components were characterized by VEGF mRNA amplification assessed by in situ hybridization in our study. A higher amplification score was observed in epithelium from recurrent pterygium, especially located in the basal and suprabasal epithelial cells. CONCLUSIONS: Based on our findings we consider that in situ hybridization assessment of VEGF for human pterygium specimens can be a useful tool for reconsidering the selection of pterygium patients to be enrolled in anti-VEGF therapy.

Endothelial cell proliferation and vascular patterns in urothelial carcinoma.

INTRODUCTION: The bladder cancer has some characteristics: the sixth most incident neoplasm in the United States, the majority of diagnosed cases in those 55 years of age and older, four times more common in man than women, a reduced five-year survival rate in case of metastatic disease. Despite the beneficial effects of the combination therapy and immunotherapy, the low response rate and drug resistance were reported. The main goal of this work was evaluation of the endothelial cell proliferation from urothelial carcinomas. PATIENTS, MATERIALS AND METHODS: Fifty-two cases of T2-T4 infiltrative bladder tumors, aged between 46 and 78 years, were investigated. Morphological, simple and cluster of differentiation 31 (CD31)∕Ki67, CD31∕smooth muscle actin (SMA) double immunostaining were performed. RESULTS: In all the analyzed infiltrative bladder tumors, three types of vessels were noticed: immature, intermediate and mature. In the central part of the tumor area, the following distribution of vessel types was noticed: immature (62.25%), intermediate (35.1%), and mature vessels (2.65%). In the peripheral tumor area, the intermediate vessels increase numerically, up to 54% and the mature ones, up to 18.6%. The peritumoral area was characterized by the absence of immature vessels and the presence of intermediate and mature ones only. It was found the presence of endothelial cell nuclei stained for Ki67 only for immature and intermediate vessels, and never for mature ones. CONCLUSIONS: The vascular patterns may contribute to a better stratification of the patient subgroups and antiangiogenic treatment algorithms.

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.

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.

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.

DNA damage in human pterygium: one-shot multiple targets.

PURPOSE: Little is known about DNA damage in human pterygium, and no data about DNA damage involvement as a potential angiogenic factor are available. We studied, with immunohistochemistry, the presence and localization of thymine dimers in the epithelial and stromal components of the human primary pterygium and its recurrences with a special emphasis on the vascular network and its interactions with the p53 tumor suppressor gene protein. METHODS: Thirty-five primary human pterygium, three recurrences, and three normal bulbar conjunctiva were included in the present study. Formalin-fixed, paraffin-embedded tissues were submitted for immunohistochemical analysis with antithymine dimers and p53 antibodies. Thymine dimer and p53 nuclear staining was assessed in the epithelial and stromal components of pterygial tissues and normal counterparts. RESULTS: Thymine dimers were present in the epithelial and stromal components of human pterygium and its recurrences. The thymine dimers were detected in the epithelial component of the human pterygium with a higher density and intensity in the basal layer of the epithelium. Small blood vessels' endothelial cells showed positive reaction for antithymine dimer antibodies together with isolated positive expression found in the nuclei of perivascular cells. For the recurrent pterygium, dimer expression was found only in the subepithelial fibrovascular layer components and in scattered cells from the basal layer of the epithelium. P53 expression was positive in 38.5% of the cases in the epithelial compartment, and in two cases, scattered p53 positive endothelial, fibroblast-like, and perivascular cells were detected in the fibrovascular compartment. CONCLUSIONS: Thymine dimers in human pterygium and its recurrences suggest that DNA damage is involved not only in pterygium epithelial and fibrous proliferation but also in angiogenesis and lymphangiogenesis from this ocular lesion in a still incomplete elucidated pathogenic mechanism.

Vascular Endothelial Growth Factor Family and Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer characterized by increased angiogenesis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and has not been extensively studied in HNSCC. This review aimed to provide a comprehensive overview of the VEGF family and its involvement in HNSCC. It discusses the significance of angiogenesis in HNSCC and the potential implications of VEGF family members, including VEGF-A, VEGF-B, VEGF-C, and VEGF-D, in tumor progression and angiogenic processes. The review highlights the need for further investigation to elucidate the specific functions and therapeutic implications of the VEGF family in HNSCC, which can ultimately contribute to development of novel therapeutic strategies for this type of cancer.

Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview.

In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.

Human Periapical Odontogenic Granulomas: Aspects of Microvessel Density (MVD), Heterogeneity of Blood Vessels and Mast Cells Density (MCD).

Periapical odontogenic granulomas are among the most encountered pathology that involve the alveolar bone, with severe consequences such as bone resorption, the presence of inflammatory infiltrate and the formation of abnormal vascularization. The present study aimed to quantify the existence of the microvessel density (MVD), mast cell density (MCD) and heterogeneity of the encountered blood vessels. A total of 37 patients diagnosed with odontogenic periapical granulomas were included, and the gender distribution, age and localization of the pathological lesions was assessed. After the surgical removal of the periapical odontogenic granuloma, the collected tissue was fixed in 10% buffered formalin. Primary processing, morphological analysis and immunohistochemical staining was performed in order to characterize the altered tissue. The results outlined the presence of a high number of mast cells, especially in the area of the inflamed tissue; the high heterogeneity of the blood vessels; and increased MVD with positive CD34. The conclusions of the study focus on the key role of the mast cells and their implication in the initiation and development of the angiogenesis process, triggering the inflammatory response of the host. Nevertheless, periapical odontogenic granulomas develop as an inflammatory response to the interaction between the host's immune system and microbial invasion.

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.

Loss of E-Cadherin Expression Correlates With Ki-67 in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The aim of the study was to evaluate the correlation between the rate of proliferation and immunohistochemical expression of E-cadherin, and their predictive role in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Samples were collected from 50 patients with HNSCC, and the expression of Ki-67 and E-cadherin was evaluated by immunohisto-chemistry (IHC). Previously, samples were conventionally stained with haematoxylin and eosin for histological diagnosis and grade. RESULTS: High E-cadherin expression was predominantly associated with less differentiated tumours (p<0.5; p=0.0305). Also, we observed a significant correlation between Ki-67 expression in tumour cells and tumour grade (p=0.0245). A strong correlation was noticed between low E-cadherin expression, increased Ki-67-proliferation rate and advanced T2-T3 tumour stage (p=0.0242). CONCLUSION: In this study we showed that Ki-67 proliferation rate and E-cadherin expression are important features in patients with HNSCC. Therefore, higher Ki-67 index values correlate with loss of E-cadherin expression, which indicates a poorer prognosis. These aspects support the use of both Ki-67 and E-cadherin as prognostic markers in specimens from patients with HNSCC.