Immunoexpression of Ki67, P16 and Beta-catenin in precursor lesions of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, after basal cell carcinoma, representing about 10-20% of all malignant skin tumors. The mortality rates of CSCC approach those of renal and oropharyngeal carcinomas, as well as melanoma, with the increasing of the risk once metastases and perineural invasion occur. Both actinic keratosis (AK) and Bowen's disease (BD) are direct precursors with the potential for progression to CSCC. In this study, we analyzed the expression of Ki67, P16 and Beta-catenin in the precursor lesions of CSCC in relation to histological prognostic parameters, respectively between them, with the aim of identifying possible correlations with a role in prognosis. Ki67 and P16 presented higher scores in advanced precancerous lesions, such as keratinocyte intraepithelial neoplasia (KIN) III and BD and low scores in seborrheic keratosis (SK). The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Statical Association between Clinical and Histopathological Parameters for Keratinocyte Carcinomas.

The most common tumor of the western world is comprised of forms of non-melanoma skin cancers, previously known as keratinocyte carcinomas (KCs) The purpose of this study was to determine de incidence of non-melanoma skin tumors and the relationship between histopathological risk factors in patients with skin cancers. The study was composed from 332 cases of skin malignancies for which clinical and histopathological aggressivity factors were statistically analyzed through comparison tests and also stored digitally. For basal cell carcinoma (BCC) statistical analysis indicated significant relationships between pT category and gender, tumor size, ulceration, depth of invasion and positive resection limits. For squamous cell carcinoma (SCC) statistical analysis indicated significant relationships between pT category and tumor size, depth of invasion and positive resection limits. Clinical and histological analysis of certain characteristics of the above-mentioned skin cancers is an essential step in documenting and improving both prognosis and therapy standards.

The role of cell adhesion molecules in the progression of bladder urothelial carcinomas.

Alteration of the intercellular adhesion system plays an essential role in the initiation and progression of bladder carcinomas. We followed the immunoexpression of adhesion molecules, E-cadherin, ß-catenin and Claudin-1, in relation to the histopathological grade and the pT category in a number of 50 urothelial carcinomas of the bladder, based on a final staining score (FSS), calculated on the basis of reaction intensity and labeled cells number. E-cadherin immunoexpression was identified in the membrane of tumor cells, low FSS being associated with invasive high-grade carcinomas. ß-catenin reactions were membranous in the case of low-grade noninvasive carcinomas and predominantly cytoplasmic and nuclear in the case of high-grade invasive ones, for which high FSS were associated. Claudin-1 was identified at the membrane level, the high FSS values being more frequent in the case of high-grade invasive carcinomas, although there were no significant statistical associations. Loss of E-cadherin expression and the associated positive linear relation of ß-catenin and Claudin-1 indicate the usefulness of the analyzed markers in identifying the invasive aggressive phenotype of urothelial bladder carcinomas.

E-Cadherin Modulation and Inter-Cellular Trafficking in Tubular Gastric Adenocarcinoma: A High-Resolution Microscopy Pilot Study.

Despite the numerous advances in tumor molecular biology and chemotherapy options, gastric adenocarcinoma is still the most frequent form of gastric cancer. One of the core proteins that regulates inter-cellular adhesion, E-cadherin plays important roles in tumorigenesis as well as in tumor progression; however, the exact expression changes and modulation that occur in gastric cancer are not yet fully understood. In an attempt to estimate if the synthesis/degradation balance matches the final membrane expression of this adhesion molecule in cancer tissue, we assessed the proportion of E-cadherin that is found in the Golgi vesicles as well as in the lysosomal pathway We utilized archived tissue fragments from 18 patients with well and poorly differentiated intestinal types of gastric cancer and 5 samples of normal gastric mucosa, by using high-magnification multispectral microscopy and high-resolution fluorescence deconvolution microscopy. Our data showed that E-cadherin is not only expressed in the membrane, but also in the cytoplasm of normal and tumor gastric epithelia. E-cadherin colocalization with the Golgian vesicles seemed to be increasing with less differentiated tumors, while co-localization with the lysosomal system decreased in tumor tissue; however, the membrane expression of the adhesion molecule clearly dropped from well to poorly differentiated tumors. Thus E-cadherin seems to be more abundantly synthetized than eliminated via lysosomes/exosomes in less differentiated tumors, suggesting that post-translational modifications, such as cleavage, conformational inactivation, or exocytosis, are responsible for the net drop of E-cadherin at the level of the membrane in more anaplastic tumors. This behavior is in perfect accordance with the concept of partial epithelial-to-mesenchymal transition (P-EMT), when the E-cadherin expression of tumor cells is in fact not downregulated but redistributed away from the membrane in recycling vesicles. Moreover, our high-resolution deconvolution microscopy study showed for the first time, at the tissue level, the presence of Lysosome-associated membrane glycoprotein 1 (LAMP1)-positive exosomes/multivesicular bodies being trafficked across the membranes of tumor epithelial cells. Altogether, a myriad of putative modulatory pathways is available as a treatment turning point, even if we are to only consider the metabolism of membrane E-cadherin regulation. Future super-resolution microscopy studies are needed to clarify the extent of lysosome/exosome exchange between tumor cells and with the surrounding stroma, in histopathology samples or even in vivo.

Subtle Immunoreactivity Differences in the Fractal Patterns of Membrane E-Cadherin in Gastric Adenocarcinoma.

Gastric cancer continues to be a significant malignancy worldwide, accounting for approximately one million new cases in 2020. Scientists are focusing on the cancerous cells' plasma membrane (PM) as a potential therapeutic target in cancer because it functions as the cell's interface with its environment through a variety of mechanisms. The capacity of membrane shape and its structures to influence biological processes frequently occurs through the regulation of enzymes or preferential protein binding to membranes via membrane shape changes. We aimed here to assess the morphological irregularities of the cellular membranes in gastric adenocarcinoma tumors, and to find any putative differences from normal gastric mucosae epithelial cells. We analyzed the pattern of E-cadherin at the level of the cell membrane using the fractal dimension (FD) analysis on fluorescence immunohistochemistry samples labeled with E-cadherin in gastric well/moderate and solid gastric adenocarcinoma from patients without any associated chemotherapeutic treatment or radiotherapy. Images were binarized based on a fixed threshold of the E-cadherin fluorescence channel, and then the FD of the binarized image outlines has been calculated in order to assess the ruggedness of the cellular membranes. Overall assessment of the FD revealed that the subtle membrane variations were evident enough to deem a statistically significant difference and the complexity of the membrane roughness was clearly higher for adenocarcinoma cases. We intended to evaluate if separating adenocarcinoma cases as low grade (G1 and G2) and high grade (G3 and solid), FD analysis could still differentiate membrane patterns and check if the available clinical parameters like age, gender, tumor location, lymph ganglia involved might correlate with FD values for adenocarcinoma patients. Altogether, the morphological analysis of a simple marker for the cell membrane can identify and distinguish tumor cells. Although there was a limited correlation between this analysis and the main clinical and pathological indicators of the disease, it will be very useful in the future for automatic computer-assisted diagnosis on slides, as well as for evaluating cellular adhesion and inter-cellular trafficking in cancer cells.

Immunohistochemical evaluation of D2-40, Galectin-3, Maspin and MCM7 expression in palate squamous cell carcinomas.

Squamous cell carcinoma (SCC) is the most frequent cancer in oral cavity and its prognosis has exhibited little improvement in the last decades. Although much less common palate SCCs manifests a higher local aggression invading very quickly the adjacent muscles and jawbones, thus being able frequently to lead to dysfunctions in chewing, swallowing, and speech. To elucidate what underlies such local aggression, we investigated the immunohistochemical expression in palate SCCs of Podoplanin (D2-40), Galectin-3 (Gal-3), mammary serine protease inhibitor (Maspin) and minichromosome maintenance complex component 7 (MCM7), markers that are known to be involved in tumor invasiveness. We found a progressive increase in reactivity for D2-40 and MCM7 from the normal epithelium toward dysplastic epithelium and respectively to SCC, which suggests the intervention of these markers in the early stages of squamous cell carcinogenesis in the palate. The highest D2-40, Gal-3 and MCM7 reactivity was observed in basaloid and in poorly differentiated (G3) palate SCCs, while for Maspin the well-differentiated (G1) palate SCCs were the most reactive. The first three markers mentioned above were most intensely expressed at the invasion front, while the Maspin reactivity was low or absent at this level. Statistically, we found significant stratification on localization, grading, muscle invasion, and survival for all investigated markers, but with very high direct correlations between D2-40, Gal-3, and MCM7 immunoreactive score (IRS) values, while between the Maspin and each of the previous markers there were very high inverse correlations. Overall, all these investigate markers proved to be responsible for the local invasiveness and regional lymph node metastasis, thus allowing a prognostic and therapeutic stratification of patients with palate SCCs.

Immunophenotypical alterations with impact on the epithelial-mesenchymal transition (EMT) process in salivary gland adenoid cystic carcinomas.

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary glands neoplasms with an indolent clinical course, slow-growing but locally aggressive and quite often with delayed recurrence and distant metastasis. In order to elucidate this tumoral behavior, we conducted an immunohistochemical study investigating the alterations of epithelial phenotype with anti-cytokeratin (CK) AE1∕AE3 and anti-E-cadherin antibodies, and the acquisition of mesenchymal phenotype with vimentin, fibronectin, N-cadherin and P-cadherin in salivary ACCs. Thus, we recorded a reduction of CK AE1∕AE3, E-cadherin, P-cadherin and fibronectin reactivity in the solid variant and especially in the cells from the periphery of invasive neoplastic proliferations, regardless histological type. These phenotypical alterations suggest the involvement of the epithelial-mesenchymal transition (EMT) process in the progression of salivary ACCs.

Adenoid Cystic Carcinoma of Salivary Gland: A Ten-Year Single Institute Experience.

Adenoid cystic carcinoma is a rare tumor, accounting for about 7.5% of all salivary gland neoplasms. More frequent developing in minor salivary gland, this is a slow-growing tumor with a long-lasting natural evolution, quite aggressive locally, but which has a tendency toward local recurrence and even for distant metastasis. We conducted a retrospective study limited to a period of 10 years in a single medical institution to investigate the morphoclinical profile of this tumor. Thus, we have established that about 60% of the tumors developed in men, with near 40% of the cases in patients in the sixth decade and, most common, the pathology affected the parotid and minor salivary glands from the hard palate mucosa. Histopathologically, prevailed the solid variant, with 72% cases presenting perineural invasion, and 41% cases showing positive surgical resection margins. Most cases had a long-standing asymptomatic evolution, so that at the time of diagnosis, more than two thirds of the patients were at least in stage II-pTNM, and in one-fifth of the cases histopathology showed lymph nodes disseminations.

Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats.

Let alone calorie restriction, life span extension in higher organisms has proven to be difficult to achieve using simple drugs. Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. However, younger subjects (< 40 years of age) are infrequently prescribed nor self-medicating with antiaging drugs. Therefore, in the present study, we aimed at assessing the effect of long-term treatment with spermidine given in the drinking water on behavioral performance and longevity of male, middle-aged Sprague-Dawley rats. We report that spermidine given in the drinking water did not extend neither the median nor the maximum life span of the middle-aged male Sprague-Dawley rats. However, spermidine treatment had a beneficial effect on the body weight and the kidney tubules, liver, and heart morphology. Behaviorally, spermidine led to a reduction in anxiety and an increase in curiosity, as assessed by exploratory behavior. Moreover, long-term treatment with spermidine enhanced autophagy in the brain and led to a diminished expression of the inflammatory markers, Tgfb, CD11b, Fcgr1, Stat1, CR3, and GFAP mRNAs in several cortical region and hippocampus of the treated rats suggesting that one beneficial effect of the long-term treatment with spermidine is an attenuated proinflammatory state in the aged brain. Our results suggest that long-term treatment with spermidine increases health span of middle-aged rats by attenuating neuroinflammation and improving anxiety and exploratory behavior.

Analysis of the distribution and expression of some tumor invasiveness markers in palate squamous cell carcinomas.

Oral cancer remains an important global health issue and despite recent diagnostic and therapeutic advances, it continues to have an unfavorable prognostic and decreased survival. Although palatal tumors represent one of the rarest locations of oral squamous cell carcinomas (SCCs), they are among the most aggressive local tumors, leaving behind important morpho-functional disabilities. In order to explain such local aggressiveness, the present study aims to investigate the immunohistochemical expression in palate SCCs of some markers known to be involved in the process of tumor invasiveness, such as Wiskott-Aldrich syndrome like (WASL), Claudin-1 (CLDN1), Integrin beta-6 (ITGB6) and c-Mesenchymal to epithelial transition protein (c-Met). We have found here a higher tumor WASL and CLDN1 reactivity in well-differentiated (G1) palate SCCs, and regardless the histological type, degree of differentiation or tumor topography, an overexpression at the invasion front, and in those palate' SCC cases with muscular invasiveness and with lymph node (LN) dissemination. ITGB6 and c-Met had a higher reactivity in moderately differentiated (G2) palate SCCs, especially at the periphery of tumor proliferations, at the invasion front and in those high invasive cases and as well as in those that associated LN dissemination. All four investigated markers were also positive at the level of LN metastatic proliferations. None of the markers could statistically stratify on age group and pain, and on bone and perineural invasion while all of them statistically stratified on survival and grading. We concluded that these markers have a prognostic role allowing the identification of those cases with an unfavorable clinical evolution and decreased survival.

The immunophenotype of epithelial to mesenchymal transition inducing transcription factors in salivary gland adenoid cystic carcinomas.

Adenoid cystic carcinoma (ACC) is the second most common malignant salivary glands neoplasms with a controversial biological behavior. Even though these tumors grow slowly, they have increased potential for recurrence and distant metastasis. In order to elucidate this behavior, our study aimed to investigate the immunoexpression in such tumors of the most important transcriptional factors [Twist, Snail, Slug, and zinc finger E-box binding homeobox 1 (ZEB1)] involved in the epithelial-mesenchymal transition process. The highest level of expression was recorded for Twist, present in all the investigated cases, followed by the Slug and Snail, while no tumor parenchyma reactivity was noticed for the ZEB1 factor. There were tumor reactivity differences regarding topography, histopathological variant, and nerve and lymph node invasion status. Thus, tumors developed from the intraoral minor salivary glands, with solid pattern, perineural invasion, locally aggressive and with lymph node metastasis were the most reactive. Therefore, these transcription factors could be useful as prognostic biomarkers and efficient therapeutic targets in such salivary malignancies.

The role of androgen receptors in vascular and cell proliferation of the prostate adenocarcinomas.

Prostate adenocarcinoma (PA) is by incidence and prognosis a unique model for investigating the biomolecular mechanisms involved in tumor progression. In this study, we analyzed the immunoexpression of androgen receptor (AR), cluster of differentiation 105 (CD105) and Ki67 for 61 cases of PA, in relation to the main clinicopathological parameters of the lesions. The AR scores, CD105 microvessel density (MVD) and Ki67 proliferation index (PI) were significantly higher in patients with serum prostate-specific antigen (PSA) above 20 ng∕mL, in ductal, colloid and sarcomatoid types of PA, in growth patterns 4-5 or mixed, respectively in the case of high-grade advanced stage tumors, with perineural and vascular invasion, as well as in groups with a reserved prognosis. The results obtained, reflected in the positive linear correlation of AR, CD105 and Ki67 expression, indicate synchronous endocrine, angiogenic and proliferative mechanisms involved in tumor progression, which can be used to optimize the targeted tumor therapy.

Periodontal clinico-morphological changes in patients wearing old nickel-chromium and copper alloys bridges.

Elderly population frequently presents more than one prosthetic restoration realized from different types of dental alloys which, in time, suffer various alterations in the oral environment. Metallic ions are released in saliva due to its electrolytic qualities, interacting with the contact tissues. Studies regarding cytotoxicity of dental alloys are providing contradictory results. Besides biocompatibility, the microbial factor is also greatly influencing the long-term success of the prosthetic rehabilitation. This study's aim was to assess the response of the gingival tissue to nickel-chromium (Ni-Cr) and copper (Cu)-based dental casting alloys from fixed dentures present in many patients from Romania. Gingival samples were taken from 124 patients wearing fixed dental restorations made from these two types of alloys from injured areas surrounding the abutment teeth; histological specimens were prepared, fixed in 10% neutral buffered formalin, paraffin-embedded and stained with Hematoxylin-Eosin (HE). Histological analysis showed the existence of a chronic inflammatory infiltrate in the gingival chorion, necrosis areas, and vascular congestion. Various morphological alterations appeared, depending on the intensity of the inflammation and the immune response. The surface epithelium suffered a hyperplasic reaction, either limited to acanthosis or involving the whole epithelium, the release of the Cu(2+) and Ni(2+) ions from the dental alloys used in bridges and crowns being responsible for inducing gingival hyperplasia and a chronic inflammation in the areas situated around the abutment teeth. The immunohistochemical study allowed us to observe an increased number of positive cluster of differentiation 3 (CD3) T-lymphocytes in periodontium, proving that the cellular immune response is rapid and intense.

Claudin-4 Immunoexpression in Urothelial Carcinomas.

The involvement of claudins in urothelial carcinogenesis is controversial. In this study, we analyzed Claudin-4 immunoexpression in 50 cases of bladder urothelial carcinomas depending on the main prognostic parameters of the lesions represented by the tumor grade and tumor extension. Claudin-4 immunoexpression scores were significantly higher in high-grade urothelial carcinomas and in tumors with invasion in muscularis propria. The results obtained indicate the involvement of Claudin-4 in the progression of urothelial bladder carcinomas.

Palate Squamous Cell Carcinomas:A Ten-Year Single Institute Experience.

The literature date estimated that about 5% of all oral cavity cancers are hard palate cancers while soft palate cancers account for about 5-12% of oropharyngeal cancers. Although rare, usually these tumors had a more aggressively behavior than other oral cancer sites. That is why our study aimed to investigate comparatively the epidemiological, clinical and histopathological peculiarities of the two palatal sites of oral squamous cell carcinomas. We conducted a retrospective study limited to a period of 10 years in a single medical institution to investigate the morphoclinical profile of such tumors. We found that patients with hard palate SCCs had an average age slightly larger compared to those who developed soft palate tumors. Also, those with hard palate tumors are mostly diagnosed in less advanced stages compared to those at the level of the soft palate, and implicitly the former had a longer survival time. Histopathologically the most encountered hard palate SCC were the conventional well-differentiated tumor, and from the peculiar SCC variant the papillary and verrucous forms while for the soft palate SCC prevailed the moderate and poor differentiated conventional SCC and from the peculiar SCC variant the basaloid and acantholytic forms. In conclusion hard palate tumors differ in many aspects from those of the soft palate, and thus specification of the origin tumor site become important for the assessment of prognosis, treatment and survival outcome of such patients.

Immunoexpression of E-cadherin, Snail and Twist in colonic adenocarcinomas.

Epithelial-mesenchymal transition (EMT) is an important mechanism in tumor progression. Snail is a transcription factor, expressed in cells which have undergone almost complete EMT and have left the tumor, and Twist is considered important in the process of metastasis, both playing a major role in EMT by indirect inhibition of E-cadherin. The study analyzed the immunoexpression of E-cadherin, Snail and Twist in 46 cases of colonic carcinomas in comparison with some histopathological prognostic factors. The quantification of reactions was done by using a composite score (CS) resulted from multiplying the percentage of marked cells with the intensity of immunostaining. The majority of cases were moderately differentiated tumors, corresponded to stage III, with vascular and perineural invasion. All cases presented positive cytoplasmic and nuclear signals for Snail and Twist. The immunostaining for both markers was intense, with the highest values of CS in G2 and G3 advanced, invasive vascular colonic carcinomas, in comparison with G1, early stage lesions. We found positive significant linear correlation of Snail and Twist expression. The results obtained indicate the implication of Snail and Twist in colonic carcinoma aggressiveness, useful aspect in the oncological evaluation of patients and guided therapy.

Immunoexpression of E-cadherin, P-cadherin and fibronectin in gastric carcinomas.

One of the mechanisms involved in gastric carcinomas progression is represented by epithelial-mesenchymal transition (EMT), a complex process during which tumor cells acquire an invasive and migratory mesenchymal phenotype. In this study, we analyzed the immunoexpression of E-cadherin, P-cadherin and fibronectin in 50 gastric carcinomas, in relation with the tumoral type, differentiation grade and lesions stage. The reactions presented variable patterns related to lesions stage. Membrane and cytoplasmic reactions were present in 62% of cases for E-cadherin and in 56% of cases for P-cadherin, being present only cytoplasmic in 34% of cases for fibronectin. The immunoexpression for E-cadherin and P-cadherin was superior in tubular gastric carcinomas, of low grade and early stage, while fibronectin expression was superior in discohesive or mixed gastric carcinomas, of high grade and in advanced stages. Negative E-∕P-cadherin and positive fibronectin immunophenotype may be associated with aggressive gastric carcinomas and supports the EMT involvement in gastric carcinogenesis.

The prognostic value of CXCR4, MMP-2 and MMP-9 in tongue squamous carcinoma.

Currently, tongue squamous cancer appears to be more frequent, especially among adults under the age of 45. Approximately 50% of these patients are diagnosed late, with clinically detectable metastases; the five-year survival rate of patients with loco-regional metastases is less than 60%. In order to explain this behavior, many investigations have been conducted in recent years, most of them focusing on identification of potential prognostic and therapeutic markers involved in the pathogenesis of tongue cancers. Our research follows the same trend, which aims to study the prognostic implications of immunohistochemical (IHC) expression of markers C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase (MMP)-2 and MMP-9 in 54 cases of tongue squamous carcinoma. The cases were selected from the archives of the Laboratory of Pathology, Emergency County Hospital, Craiova, Romania, from the 2015-2017 period. They were immunohistochemically processed using the labeled Streptavidin-Biotin (LSAB) enzyme detection technique, and as a method of evaluating reactions, the IHC score developed by Remmele & Stegner. Reactivity for the investigated markers was recorded in both primary tumors, parenchymal and stromal, and in lymph node metastases, and also in normal or dysplastic mucosa adjacent to tumor lesions. The maximum tumor reactivity was recorded for CXCR4, followed by MMP-9 and MMP-2. In addition, all of these markers were expressed stronger in the invasion front and especially in the lymph node metastatic forms. This immunoprofile would suggest their implication in loco-regional invasion and dissemination processes, allowing the selection of the most aggressive forms of tongue squamous carcinoma.

Immunoexpression of MMP-8, MMP-9 and TIMP-2 in dilated cardiomyopathy.

Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. In this study, we determined the MMP-8, MMP-9 and TIMP-2 immunoexpression in the heart of patients diagnosed with DCM in relation to a histological composite score (HCS). The study included 40 cases of heart fragments that were processed by the usual paraffin inclusion technique, followed by a semi-quantitative evaluation of histopathological parameters, which summed, allowed the establishment of a HCS. Subsequently, the cases were immunohistochemically processed for MMP-8, MMP-9 and TIMP-2, followed by the semi-quantitative evaluation of their expression intensity. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS. In case of MMP-9, the immunostaining intensity analysis in relation to the HCS level revealed insignificant differences, but we found an association of increased and moderate intensity with low HCS. The imbalance between TIMPs and MMPs disrupts the ECM architecture and contributes to the remodeling process in DCM, aspect that can be used in the development of new clinical therapies.

SMAD4 and TGFßR2 expression in pancreatic ductal carcinoma.

Pancreatic ductal carcinoma is the most common type of pancreatic cancer, and currently represents the fourth cause of death by cancer, worldwide. Among classical pancreatic markers that ascertain the histopathology, new emerging targets have been proposed for both diagnostic and prognostic purposes. In the present study, utilizing a group of 28 confirmed resected pancreatic ductal carcinomas, we have assessed the immunoexpression and correlation ratios of mothers against decapentaplegic homolog 4 (Drosophila) (SMAD4)∕transforming growth factor beta receptor 2 (TGFßR2), and vimentin∕cluster of differentiation 105 (CD105). SMAD4 showed an overall increase in tumors versus pancreatic control tissue, but a decrease from G1 towards poorly differentiated tumors, while TGFßR2, vimentin and CD105 showed higher expression values in the tumor areas. Vimentin-CD105 colocalization degree decreased in tumor tissues compared to controls, illustrating a desynchronization of these two markers, both of them being negative in the tumor epithelia. Altogether, it is highly plausible that all these key players revolve around the epithelial-to-mesenchymal transition phenomenon, and this itself modulates the clinical outcome of the patient.