Gastric-Type Expression Signature in Hepatocellular Carcinoma.

It is known that V-set and immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule that can serve as an indicator of better survival in patients with gastric cancer. Its interaction with cytoplasmic thyroid transcription factor 1 (TTF-1) has been hypothesized to characterize gastric-type HCC, but its clinical importance is far from understood. As VSIG1 has also been supposed to be involved in the epithelial-mesenchymal transition (EMT) phenomenon, we checked for the first time in the literature the supposed interaction between VSIG1, TTF-1, and Vimentin (VIM) in HCCs. Immunohistochemical (IHC) stains were performed on 217 paraffin-embedded tissue samples that included tumor cells and normal hepatocytes, which served as positive internal controls. VSIG1 positivity was seen in 113 cases (52.07%). In 71 out of 217 HCCs (32.71%), simultaneous positivity for VSIG1 and TTF-1 was seen, being more specific for G1/G2 carcinomas with a trabecular architecture and a longer OS (p = 0.004). A negative association with VIM was revealed (p < 0.0001). Scirrhous-type HCC proved negative for all three examined markers. The present paper validates the hypothesis of the existence of a gastric-type HCC, which shows a glandular-like architecture and is characterized by double positivity for VSIG1 and TTF-1, vimentin negativity, and a significant OS.

Combined hepatocellular-cholangiocarcinoma: from genesis to molecular pathways and therapeutic strategies.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. Little is known about the combined hepatocellular-cholangiocarcinoma (cHCC-ICC) variant and the proper therapeutic strategies. Out of over 1200 available studies about cHCC-ICC, we selected the most representative ones that reflected updated information with application to individualized therapy. Based on literature data and own experience, we hypothesize that two molecular groups of cHCC-ICC can be identified. The proposed division might have a significant therapeutic role. Most cases develop, like HCC, on a background of cirrhosis and hepatitis and share characteristics with HCC; thus, they are named HCC-type cHCC-ICC and therapeutic strategies might be like those for HCC. This review also highlights a new carcinogenic perspective and identifies, based on literature data and the own experience, a second variant of cHCC-ICC called ICC-type cHCC-ICC. Contrary to HCC, these cases show a tendency for lymph node metastases and ICC components in the metastatic tissues. No guidelines have been established yet for such cases. Individualized therapy should be, however, oriented toward the immunoprofile of the primary tumor and metastatic cells, and different therapeutic strategies should be used in patients with HCC- versus ICC-type cHCC-ICC.

HPV disrupt the cytoskeleton in oral squamous cell carcinomas from non-oropharyngeal sites via the E-cadherin/Mena/SMA pathway.

In this paper, we aimed to evaluate the mechanism of actin cytoskeleton disruption, in oral squamous cell carcinoma (OSCC). A total of 43 patients with surgically resected OSCCs located in non-oropharyngeal regions were randomly selected. The expression of E-cadherin, ß-catenin, smooth muscle actin (SMA), Mena, maspin, V-set and immunoglobulin domain containing 1 (VSIG1), ß human chorionic gonadotropin (ßhCG), and angiotensin-converting enzyme (ACE) was assessed via immunohistochemistry (IHC) and evaluated in association with the prevalence of high-risk human papillomavirus (HPV). Mena positivity (n = 30; 69.77%) was more frequent in poorly differentiated OSCC of the tongue and lips with high-risk HPV viral DNA and a lymph node ratio (LNR) ≤ 2.5. Loss of E-cadherin was more prevalent among poorly differentiated stage pT4N1 tumors with an LNR ≤ 2.5 and perineural invasion. These cases were classified as SMA-high tumors. Independent negative prognostic factors included high Mena expression, loss of E-cadherin, high SMA expression, and the presence of high-risk HPV. No VSIG1 positivity was observed. In conclusion, in non-oropharyngeal OSCC, cytoskeleton activity might be driven by the Mena/E-cadherin/SMA axis, reflecting active epithelial-mesenchymal interaction. High Mena intensity is an indicator of poorly differentiated carcinomas with high-risk HPV and unfavorable prognosis.

A Rare Case of Histopathologically Confirmed Creutzfeldt-Jakob Disease from Romania, Long Route to Diagnosis-Case Report and an Overview of the Romanian CJD Situation.

Creutzfeldt-Jacob disease is a progressive and ultimately fatal disease, representing one of the most common forms of prion diseases. It is a rare pathology presenting with various symptomatology, and the fact that a definite diagnosis can be obtained solely by neuropathological techniques makes it hard to recognize and diagnose. Here we present the clinical and neuropathological features of a 72-year-old woman, who originally presented in a county hospital, then, along with the disease progression, got transferred to a university center in Romania, where CJD-specific tests are rarely performed, and ultimately was diagnosed with the help of international collaboration. The purpose of this case report and review is to summarize the Romanian CJD situation until the present day, to place the Romanian CJD epidemiology in an Eastern European context, and to highlight the diagnostic options and possibilities for clinical practitioners. We would also like to draw attention to the need for a national surveillance system. By presenting the patient's route in Romania from the first presentation to diagnosis, we would like to emphasize the importance of interdisciplinary and international collaboration, by which we managed to cross the regional diagnostic boundaries and create a possible diagnostic pathway for future cases.

From Dukes-MAC Staging System to Molecular Classification: Evolving Concepts in Colorectal Cancer.

This historical review aimed to summarize the main changes that colorectal carcinoma (CRC) staging systems suffered over time, starting from the creation of the classical Duke's classification, modified Astler-Coller staging, internationally used TNM (T-primary tumor, N-regional lymph nodes' status, M-distant metastases) staging system, and ending with molecular classifications and epithelial-mesenchymal transition (EMT) concept. Besides currently used staging parameters, this paper briefly presents the author's contribution in creating an immunohistochemical (IHC)-based molecular classification of CRC. It refers to the identification of three molecular groups of CRCs (epithelial, mesenchymal and hybrid) based on the IHC markers E-cadherin, ß-catenin, maspin, and vimentin. Maspin is a novel IHC antibody helpful for tumor budding assessment, which role depends on its subcellular localization (cytoplasm vs. nuclei). The long road of updating the staging criteria for CRC has not come to an end. The newest prognostic biomarkers, aimed to be included in the molecular classifications, exert predictive roles, and become more and more important for targeted therapy decisions.

In-House Validated Map of Lymph Node Stations in a Prospective Cohort of Colorectal Cancer: A Tool for a Better Preoperative Staging.

Preoperative staging of colorectal cancer (CRC) based on imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is crucial for identification and then removal of the positive lymph nodes (LNs). The aim of this study was to evaluate the correlation between preoperatively seen morphologic criteria (number, size, shape, structure, borders, or enhancement patterns) and histopathological features of LNs using an in-house validated map of nodal stations. A total of 112 patients with CRC that underwent surgery were preoperatively evaluated by CT scans. The locoregional, intermediate, and central LNs were CT-mapped and then removed during open laparotomy and examined under microscope. The analysis of correlations was interpreted using the suspicious-to-positive ratio (SPR) parameter. The greatest correlation was found in tumors located in the sigmoid colon, descending colon and middle rectum; SPR value was 1.12, 1.18, and 1.26, respectively. SPR proved to be 0.59 for cases of the transverse colon. Regarding the enhancement type, the dotted pattern was mostly correlated with metastatic LNs (OR: 7.84; p < 0.0001), while the homogenous pattern proved a reliable indicator of nonmetastatic LNs (OR: 1.99; p < 0.05). A total of 1809 LNs were harvested, with a median value of 15 ± 1.34 LNs/case. Transdisciplinary approach of CRC focused on pre-, intra-, and postoperatively mapping of LNs might increase the accuracy of detecting metastasized nodes for tumors of the distal colon and middle rectum but not for those of the transverse colon. In addition to morphologic criteria, the enhancement pattern of LNs can be used as a predictor of nodal involvement improving the CT-based preoperative staging.

Staphylococcus-induced proliferative glomerulonephritis and cerebral hemorrhage - fatal complications in a young female with postpartum cardiomyopathy and an implanted left ventricular assist device: a case report and review of the literature.

Background: The continuous-flow left ventricular assist device (CF-LVAD) is used to save the lives of patients in the final stage of congestive heart failure, replacing the pump function of the left ventricle. Although quality of life increases significantly, CF-LVAD-related complications might prove fatal, as in the case presented in this paper.Methods: A 20-year-old female, during her second pregnancy, presented with signs of heart failure. Emergency caesarean section was necessary to save the baby, but peripartum cardiomyopathy developed in the mother. The use of an implantable cardioverter-defibrillator (ICD) was necessary 5 years later. As the clinical progression was unfavorable under medical treatment, with the patient reaching INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) Profile 1 (refractory cardiogenic shock), the treatment of choice was the implantation of a CF-LVAD.Results: After 3 years of follow-up (at the age of 28), the patient presented with a positive hemoculture for Staphylococcus aureus. Prolonged antibiotic therapy and attentive follow-up was prescribed. Although an effective antiplatelet and anticoagulant treatment was applied, and despite therapeutic values of prothrombin time and international normalized ratio (INR), the patient died as result of a fatal cerebral hemorrhage. The autopsy also revealed septic emboli, disseminated intravascular coagulation, and focal proliferative glomerulonephritis.Conclusions: Although the benefits of CF-LVAD are significant, bleeding episodes can be severe and LVAD-associated infection can trigger glomerular injury and increase mortality.

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity-The Main Keys for Optimal Approach.

BACKGROUND: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. METHODS: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers ß-catenin and E-cadherin, same as KRAS and BRAF mutations. RESULTS: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. CONCLUSIONS: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors.

Cystic low-grade collecting duct renal carcinoma with liver compression - A challenging diagnosis and therapy: A case report.

BACKGROUND: A collecting duct carcinoma is a very rare, malignant renal epithelial tumor. Distant metastases are present in one third of cases at the time of diagnosis. It is known to have a poor prognosis. CASE SUMMARY: A 42-year-old male was sent to our surgery clinic for removal of a 119.2 mm × 108.3 mm encapsulated cystic mass, which was localized in the 8th segment of the right liver lobe. The lesion was first identified on ultrasonography. A computed tomography scan confirmed the presence of a Bosniak type III cystic lesion, which affected the liver and convexity of the right kidney. Surgical intervention involved a right nephrectomy, with removal of the cystic mass. The patient was mobilized on the first postoperative day and was discharged after 7 d. The histological and immunohistochemical examination revealed a low-grade collecting duct renal carcinoma, which is a rare variant of papillary carcinoma, with low malignant potential. The patient did not receive chemotherapy and after 21 mo of follow-up, a radiological examination and laboratory analyses showed normal aspects. No relapse or other complications were reported. CONCLUSION: To manage renal tumors properly, a correct histopathological diagnosis is crucial, as is early diagnosis and correct surgical treatment.

Immunohistochemical-based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial-mesenchymal transition.

The aim of the present study was to classify colorectal carcinoma (CRC) into molecular subtypes, based on immunohistochemical (IHC) assessments. A total of 112 CRC samples were molecularly classified based on the expression levels of epithelial-mesenchymal transition (EMT)-associated IHC markers. A total of three molecular subtypes were defined: Epithelial, membrane positivity for E-cadherin and ß-catenin, negative for vimentin; mesenchymal, E-cadherin-negative, nuclear ß-catenin- and vimentin-positive; and hybrid cases, epithelial tumor core and mesenchymal tumor buds. Most of the cases were diagnosed as moderately differentiated adenocarcinoma (n=89; 79.46%). The majority of cases (n=100; 89.28%) exhibited a mismatch repair proficient status (microsatellite stable CRCs). A predominance of epithelial-type (n=51; 45.54%) and hybrid CRCs (n=47; 41.96%) was observed, whereas a few cases (n=14; 12.50%) were classified as mesenchymal-type CRCs. This molecular classification was associated with pathological stage (P<0.01), pT stage (P=0.04), pN stage (P<0.01), the grade of tumor budding (P=0.04), and maspin expression in both the tumor core (P=0.04) and the invasion front (P<0.01). The mesenchymal-type cases predominantly exhibited lymph node metastases, high-grade budding and a tendency towards maspin nuclear predominance. All epithelial-type cases with maspin-only expression (n=18) were non-metastatic. Patients with CRC of the epithelial subtype and those with a lymph node ratio (LNR) ≤0.15 presented the best overall survival, followed by those with hybrid and mesenchymal subtypes. Nuclear maspin positivity was more frequent in cases with a high-budding degree compared with those with a low-budding degree (P=0.03). The EMT-associated molecular classification of CRCs may be used to identify the most aggressive CRCs, which show a mesenchymal phenotype, high-budding degree, maspin nuclear positivity and lymph node metastases. The pN stage, LNR and budding degree of patients, which can be evaluated with maspin expression, remain the most important prognostic factors.

Interaction of arylsulfatases A and B with maspin: A possible explanation for dysregulation of tumor cell metabolism and invasive potential of colorectal cancer.

BACKGROUND: Although it has been shown that arylsulfatases are lost in colorectal cancer (CRC) cell lines, their exact role in the carcinogenesis and behavior of this cancer was not elucidated. No data about the correlation between serum and immunohistochemical (IHC) level of arylsulfatases (ARSA, ARSB) in patients with CRC were published yet. AIM: To evaluate the possible prognostic value of ARSA and/or ARSB in CRC, at circulating and protein levels. METHODS: The present study included 45 consecutive patients who were prospectively diagnosed with CRC. For IHC stains (protein expression) ARSA, ARSB and maspin expression were quantified. For these markers, cytoplasmic expression was taken into account. For gene expression study, circulating mRNA was isolated from all patients, before surgery. A group of 45 healthy patients without inflammatory or tumor pathologies was used as control group. Reverse transcription and Taqman Gene Expression Array were used for ARSB gene expression. RESULTS: The preoperative circulating RNA level of the ARSB gene was significantly decreased in patients with CRC (RQ < 1), compared with the control group (RQ > 1). A more significant decrease (RQ < 0.5) occurred in ulcero-infiltrative maspin-positive adenocarcinomas, with a higher degree of tumor budding, diagnosed in locally advanced stages (pT3/4). ARSA/maspin immunopositivity indicated a higher risk for lymph node metastasis, while triple positivity for maspin/ARSA/ARSB and ARSB gene expression level < 0.5 were indicators of CRC aggressive behavior, independent of lymph node status. CONCLUSION: The significant independent negative prognostic factors of CRC are the ulcero-infiltrative aspect, high budding degree, triple positivity for maspin, ARSA and ARSB, and low ARSB gene expression.

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, ß-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane ß-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.

DNA extraction from paraffin embedded colorectal carcinoma samples: A comparison study of manual vs automated methods, using four commercially kits.

BACKGROUND: Nucleic acid isolation from formalin-fixed, paraffin-embedded tissue (FFPET) samples is a daily routine in molecular pathology laboratories, but extraction from FFPET is not always easily achieved. Choosing the right extraction technique is key for further examinations. AIM: To compare the performance of four commercially available kits used for DNA extraction in routine practice. METHODS: DNA isolation was performed on 46 randomly selected formalin-fixed, paraffin-embedded (FFPE) colorectal adenocarcinoma (CRC) surgical specimens. Four commercially available extraction kits were used: two for manual DNA extraction (the PureLink Genomic DNA Mini Kit from Invitrogen and the High Pure FFPE DNA Isolation Kit from Roche) and two for automated DNA extraction (the iPrep Genomic DNA Kit from Invitrogen and the MagnaPure LC DNA Isolation Kit from Roche). The DNA concentration and quality (odds ratio) among the four systems were compared. The results were correlated with the clinicopathological aspects of CRC cases: age, gender, localization, macro- and microscopic features, lymph node metastases, and the lymph node ratio. RESULTS: The highest DNA concentration was obtained using the manual kits: 157.24 ± 62.99 ng/µL for the PureLink Genomic DNA Mini Kit and 86.64 ng/µL ± 43.84 for the High Pure FFPE DNA Isolation Kit (P < 0.0001). Lower concentrations were obtained with automated systems: 20.39 ± 21.19 ng/µL for the MagnaPure LC DNA Isolation Kit and 8.722 ± 6.408 ng/µL for the iPrep Genomic DNA Kit, with differences between the systems used (P < 0.0001). The comparison between age, gender, tumor localization, pT or pN stage and the lymph node ratio indicated no statistically significant difference in DNA concentration using any of the nucleic acid isolation kits. DNA concentration was influenced by the macroscopic features and grade of differentiation. A higher DNA concentration was obtained for well-differentiated polypoid colorectal adenocarcinomas (CRCs), compared with undifferentiated ulcero-infiltrative carcinomas, irrespective of the kit used. CONCLUSION: For research or diagnosis that needs high DNA concentrations, manual methods of DNA isolation should be used. A higher amount of DNA can be obtained from polypoid-type differentiated CRCs. Automated systems confer comfort and a lower amount of DNA that is, however, sufficient for classic polymerase chain reaction (PCR) and real-time quantitative PCR molecular examinations. All four commercially available kits can be successfully used in daily practice.

Angiomyofibroblastoma mimicking an inguinal hernia: a challenging diagnosis in a male patient.

INTRODUCTION: Angiomyofibroblastoma is a rare benign myofibroblastic neoplasm which mainly occurs in the soft tissues of the pelvi-perineal region of females. AIM: To present an unusual case of angiomyofibroblastoma mimicking an inguinal hernia in a 62-year-old male. MATERIAL AND METHODS: The patient was hospitalized with an irreducible, painless inguinal mass and surgical intervention for inguinal hernia was decided. The well-defined nodular mass was sent for histological examination. RESULTS: Under microscope, proliferation of spindle and oval cells around thin-walled vessels was observed, being intermingled with mature adipocytes. We did not identify necrosis, haemorrhage, cytologic atypia or mitotic figures. The tumour cells displayed positivity for desmin, vimentin, CD34, oestrogen and progesterone receptors, a low Ki67 index and unusual nuclear positivity for c-theta (PKCθ). They were negative for smooth muscle actin (SMA), S100, CD44, maspin, synaptophysin, DOG1 and CD117. The case was diagnosed as angiomyofibroblastoma, the main challenge being the differential diagnosis with aggressive angiomyxoma, which can present a similar histologic aspect and immunophenotype and recurs more frequently. No recurrences were observed 8 months after the surgery. CONCLUSIONS: Angiomyofibroblastoma should be included in the differential diagnosis of inguinal hernia. This is the fourteenth case of angiomyofibroblastoma diagnosed in males.

Gastrointestinal Carcinoma with Plasmacytoid Morphology: Positivity for c-MET, Arylsulfatase, and Markers of Epithelial-Mesenchymal Transition, as Indicators of Aggressivity.

BACKGROUND: Plasmacytoid urothelial carcinoma is a rare and aggressive histologic variant of high-grade carcinoma of the urinary bladder. Few than 250 cases have been reported in the urinary bladder till January 2019. In this paper, a case series of unusual gastrointestinal carcinomas with plasmacytoid morphology was included. Only one similar case of the stomach was previously published and no such cases were found in colon. METHODS: We present the complex immunoprofile, using a panel of 39 biomarkers, of the largest group of primary gastrointestinal carcinomas with plasmacytoid morphology reported in literature (one from upper rectum and six from stomach). RESULTS: All of the seven cases showed lymph node metastases and only one survived over 25 weeks after surgical excision. The indicators of aggressivity were age (over 60), advanced stage (from IIIA to IV), E-cadherin negativity, and vimentin positivity. The immunoprofile indicated unfavorable prognosis for mesenchymal-type carcinomas (negativity for E-cadherin and positivity for vimentin, with membrane to nuclear translocation or negativity of ß-catenin). The survivor showed an "epithelial-type adenocarcinoma with plasmacytoid dedifferentiation", with membrane positivity for E-cadherin and ß-catenin and vimentin negativity. All of the cases expressed c-MET and were negative for HER-2. CONCLUSIONS: Primary carcinoma with plasmacytoid morphology is a dedifferentiated variant of adenocarcinoma or poorly cohesive carcinomas. Vimentin positive dedifferentiated-poorly cohesive carcinomas should be considered as mesenchymal-type highly malignant carcinomas. This rare histologic variant of gastrointestinal cancer might respond to anti-c-MET tyrosine kinases.

Sentinel node biospy using intravital blue dye: An useful technique for identification of skip metastases in gastric cancer.

As the lymph node status remains the main prognostic factor of gastric cancer (GC), several lymph node-based staging systems have been recently proposed for an appropriate postoperative therapy. The identification of sentinel lymph nodes (SLNs) might improve the postoperative protocols. The aim of this study was to present our experience in detecting SLNs in GC using methylene blue dye.We have performed an observational study and retrospectively analyzed all of the consecutive cases of GC operated by the same surgical team and managed by the same pathologists during 2013 to 2015. In all of the cases SLN status was determined using the methylene blue that was intraoperatively administered in the peritumoral subserosal tissue. All blue colored nodes were histopathologically examined. In the node negative cases immunohistochemical stains using AE1/AE3 keratin were performed.The blue SLNs were identified in 48 out of the 50 cases included in the study, with a 96% sensitivity and 87.50% specificity. From the 48 cases, 34 (70.83%) presented positive SLNs; in the other 14 cases the SLNs were negative (29.17%). False negativity was observed in 6 of the 14 cases. In 2 of the cases the false negativity of the group 20 was induced by the anthracotic pigment. In other 2 false negative cases, although no regional metastases were founded, sentinel skip metastases in the group 8 and 15, respectively, were identified.Mapping of the SLNs is a simple and cheap method that might improve the accuracy of LN-based staging of patients with GC and favor identification of skip metastases.

Lymph node ratio, an independent prognostic factor for patients with stage II-III rectal carcinoma.

BACKGROUND: Identification of the proper surgical method and the most reliable prognostic parameters of rectal carcinomas is a challenging issue. The aim of this paper was to determine the possible prognostic role of the number of harvested lymph nodes versus lymph node ratio (LNR) in patients with rectal carcinomas, and the proper value of LNR that can be used as prognostic parameter. MATERIALS AND METHODS: A retrospective study was performed in 186 consecutive patients with rectal carcinomas that underwent surgical resection. The LNR was calculated for cases from stage II-III, and was correlated with classic prognostic parameters and overall survival (OS). RESULTS: A statistically significant difference was found between LNR of 0.15 and OS (p = 0.03), respectively LNR > 0.15 and TNM stage (p < 0.0001), but also tumor infiltration level (p < 0.05). The number of harvested lymph nodes was not correlated with the tumor stage (r = 0.148, p = 0.06) and this parameter did not influence the OS, when the number of 12 or 14 lymph nodes was used as the ideal value (p = 0.6 and p = 0.66, respectively). CONCLUSION: In patients with rectal carcinomas that underwent preoperative chemoradiotherapy, a LNR of 0.15 is a parameter with independent prognostic value, comparing with the number of harvested lymph nodes. The specific LNR should be calculated in larger cohorts.

The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.

BACKGROUND: Metastases to the stomach are extremely rare and the metastatic pathway is not well understood. OBJECTIVE: To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells. METHOD: The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents. RESULTS: In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, ß-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma. CONCLUSION: In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/ß-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy.

Nuclear maspin expression: A biomarker for budding assessment in colorectal cancer specimens.

AIM: To evaluate the maspin expression in colorectal carcinomas (CRC) and its possible role in quantification of the tumor budding. METHODS: The tumor budding was prospectively quantified in 49 consecutive cases of patients that underwent surgical resection for CRC. The cases were divided in two groups: group A (n=23) - low budding (<5 tumor buds per high microscopic field) and group B (n=26) - high budding CRCs (≥5 buds). Maspin expression was evaluated in the tumor core and the buds from the hot spot area in 44 of the microsatellite stable adenocarcinomas. Its expression was quantified as negative, cytoplasmic only, nuclear only or mixed expression (cytoplasm and nucleus). RESULTS: Compared with group A, a higher pT (p <0.0001) and pN stage (p=0.0001) and infiltrating aspect at macroscopic evaluation (p=0.0081) was identified in group B. No correlation between the maspin expression in the tumore core and the budding grade was noted (p=0.14). Compared with the tumor core, the cytoplasm to nuclear translocation of maspin was more frequently observed in cases from group B than A (n=0.0063). CONCLUSION: For the colorectal carcinomas, the infiltrative aspect at macroscopic evaluation and nuclear maspin in the buds might be used as indicators of risk for lymph node metastases. Maspin nuclear expression in the buds may be helpful for a proper budding assessment and may serve as a negative prognostic factor.