Browsing by Author "Briede, Inese"
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Item The association between inflammation, epithelial mesenchymal transition and stemness in colorectal carcinoma(2020-01-08) Briede, Inese; Strumfa, Ilze; Vanags, Andrejs; Gardovskis, Janis; Department of Pathology; Department of SurgeryBackground: Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence. Purpose and methods: The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC. Results: There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn’s like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007). Conclusion: High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.Item Association of Epithelial Mesenchymal Transition, Stemness and Inflammation in Colorectal Carcinoma. Doctoral Thesis(Rīga Stradiņš University, 2022) Briede, Inese; Gardovskis, Jānis; Štrumfa, IlzeColorectal cancer (CRC) and its treatment is one of the hot topics in medicine, as there is a still a high number of patients with CRC and deaths from CRC. In the era of personalized medicine, a huge field of research is devoted to inflammation, a process that plays an important dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumoural inflammation in CRC. The current theoretical background allows us to link inflammation, the epithelial-mesenchymal transition (EMT), and the closely associated stem cell differentiation in CRC. However, there is scarce direct morphological evidence. The aim of this work was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of CRC, EMT, and mismatch repair (MMR) protein expression. Materials and methods: This retrospective, morphological, and immunohistochemical investigation involved 553 consecutive cases of surgically treated CRC. Besides histopathological CRC assessment, peritumoural inflammation, EMT-characterizing molecular parameters, and MMR protein immunohistochemical detection within CRC tissue was performed. Descriptive statistical analysis was done. The research was carried out in accordance with the Declaration of Helsinki and received approval from the Committee of Ethics of Riga Stradins University [No E-9 (2), 04.09.2014].Results: The tumours of the 553 CRC cases were predominantly located in the left part of the bowel (70.9 %), and were significantly associated with an annular appearance and smaller size (p < 0.05). Mucinous and signet ring cell carcinomas detected within this study were associated with a larger tumour size and significant local structure involvement. Locally advanced tumours predominated within this study: pT3 comprised 49.6 % of cases, pT4 comprised 35.6 % of cases, and pN + comprised 40.5 % of cases. The extent of necrosis was significantly higher in tumours with higher pT, grade, and pN+. There were significant associations between high-grade inflammation and lower pT (p = 0.002), the absence of lymph node metastases (p< 0.001), and less frequent local structure involvement (p< 0.05). Expression of EMT markers and MMR proteins yielded no significant associations with peritumoural inflammation based on the Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin expression was significantly associated with the eosinophil density (p = 0.007), and lower N-cadherin expression was significantly associated with the presence of synchronous CRC. Lower MMR protein expression was associated with changes in E-cadherin and CD44 expression (p< 0.05). Lower MLH1 expression was associated with a lower neutrophil density within the CRC (p = 0.02).Conclusion: High-grade peritumoural inflammation is associated with beneficial morphologic CRC features, including less frequent invasion, and is not secondary to tissue damage and necrosis. Crohn’s disease-like lymphoid reaction (CLR) is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation based on the Klintrup-Mäkinen score and CLR are not dependent on EMT and stem cell differentiation. MMR protein expression is a marker for EMT within CRC, indicating the need to perform these tests on routine examination to detect patients who might need more advance treatment. MLH1 expression within CRC affects the density of neutrophils within peritumoural inflammation, showing a potential role for the MMR status in anti-tumour immunity. This research highlights the complex associations between inflammation, tumour morphology, EMT, and MMR protein expression in human CRC tissues.Item Association of Epithelial Mesenchymal Transition, Stemness and Inflammation in Colorectal Carcinoma. Summary of the Doctoral Thesis(Rīga Stradiņš University, 2022) Briede, Inese; Gardovskis, Jānis; Štrumfa, IlzeColorectal cancer (CRC) and its treatment is one of the hot topics in medicine, as there is a still a high number of patients with CRC and deaths from CRC. In the era of personalized medicine, a huge field of research is devoted to inflammation, a process that plays an important dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumoural inflammation in CRC. The current theoretical background allows us to link inflammation, the epithelial-mesenchymal transition (EMT), and the closely associated stem cell differentiation in CRC. However, there is scarce direct morphological evidence. The aim of this work was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of CRC, EMT, and mismatch repair (MMR) protein expression. Materials and methods: This retrospective, morphological, and immunohistochemical investigation involved 553 consecutive cases of surgically treated CRC. Besides histopathological CRC assessment, peritumoural inflammation, EMT-characterizing molecular parameters, and MMR protein immunohistochemical detection within CRC tissue was performed. Descriptive statistical analysis was done. The research was carried out in accordance with the Declaration of Helsinki and received approval from the Committee of Ethics of Riga Stradins University [No E-9 (2), 04.09.2014].Results: The tumours of the 553 CRC cases were predominantly located in the left part of the bowel (70.9 %), and were significantly associated with an annular appearance and smaller size (p < 0.05). Mucinous and signet ring cell carcinomas detected within this study were associated with a larger tumour size and significant local structure involvement. Locally advanced tumours predominated within this study: pT3 comprised 49.6 % of cases, pT4 comprised 35.6 % of cases, and pN + comprised 40.5 % of cases. The extent of necrosis was significantly higher in tumours with higher pT, grade, and pN+. There were significant associations between high-grade inflammation and lower pT (p = 0.002), the absence of lymph node metastases (p< 0.001), and less frequent local structure involvement (p< 0.05). Expression of EMT markers and MMR proteins yielded no significant associations with peritumoural inflammation based on the Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin expression was significantly associated with the eosinophil density (p = 0.007), and lower N-cadherin expression was significantly associated with the presence of synchronous CRC. Lower MMR protein expression was associated with changes in E-cadherin and CD44 expression (p< 0.05). Lower MLH1 expression was associated with a lower neutrophil density within the CRC (p = 0.02).Conclusion: High-grade peritumoural inflammation is associated with beneficial morphologic CRC features, including less frequent invasion, and is not secondary to tissue damage and necrosis. Crohn’s disease-like lymphoid reaction (CLR) is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation based on the Klintrup-Mäkinen score and CLR are not dependent on EMT and stem cell differentiation. MMR protein expression is a marker for EMT within CRC, indicating the need to perform these tests on routine examination to detect patients who might need more advance treatment. MLH1 expression within CRC affects the density of neutrophils within peritumoural inflammation, showing a potential role for the MMR status in anti-tumour immunity. This research highlights the complex associations between inflammation, tumour morphology, EMT, and MMR protein expression in human CRC tissues.Item Can intratumoural vascularisation CT contrast dynamics help differentiate malignant renal tumour subtypes?(2023) Putrins, Davis Simanis; Radzina, Maija; Liepa, Māra; Maļika- Popova, Ņina; Saule, Laura; Ratniece, Madara; Vjaters, Egils; Jukonis, Jānis; Briede, Inese; Department of Radiology; Onkoloģijas institūts; Department of PathologyItem Epiteliāli mezenhimālas transformācijas, iekaisuma un cilmes šūnu diferenciācijas saistība kolorektālā vēzī. Promocijas darba kopsavilkums(Rīgas Stradiņa universitāte, 2022) Briede, Inese; Gardovskis, Jānis; Štrumfa, IlzeKolorektālais vēzis (KRV) joprojām ir viena no aktuālākajām problēmām medicīnā, jo novērojama tā augsta izplatība un augsts nāves gadījumu skaits. Personalizētās medicīnas laikmetā arvien lielāku nozīmi pievēršot imūnajai atbildei KRV gadījumā, liela nozīme ir arī iekaisuma izpētei. Peritumorozs iekaisums, lai arī tam ir divējāda loma kanceroģenēzē, ir pierādīts kā viens no KRV prognozē nozīmīgajiem faktoriem. Teorētiskajos pētījumos ir raksturota saistība starp iekaisumu, epiteliāli mezenhimālo transformāciju un cilmes šūnu diferenciāciju KRV, bet šobrīd tam ir maz tiešu morfoloģisku pierādījumu.Šī pētījuma mērķis bija raksturot iekaisuma nozīmi kolorektālā vēzī, analizējot tā saistību ar KRV morfoloģiskajiem prognostiskajiem faktoriem, epiteliāli mezenhimālo transformāciju (EMT) un DNS labotājgēnu proteīnu ekspresiju. Materiāli un metodes. Retrospektīvā pētījumā tika izvērtēti 553 secīgi ķirurģiski operēti KRV gadījumi. Tika veikta morfoloģiska un imūnhistoķīmiska izmeklēšana, nosakot KRV morfoloģiskos parametrus, kā audzēja izplatības dziļums (pT), metastātisku limfmezglu klātesamība (pN +), invāzija lokālajās struktūrās, nekrozes plašums. Tika novērtēts peritumorozs iekaisums, kā arī EMT un DNS labotājgēnu kodējošo proteīnu raksturojošo IHĶ marķieru ekspresija KRV audos. Tika veikta deskriptīva statistiska analīze. Pētījums veikts saskaņā ar Helsinku deklarāciju un ir saņēmis Rīgas Stradiņa universitātes Ētikas komitejas atļauju (izsniegta 04.09.2014., E-9 (2)). Rezultāti. Pētījumā tika iekļauti 553 secīgi KRV gadījumi. Lielākā daļa audzēju bija lokalizēti kreisajā zarnu pusē (70,9 %), un tos raksturoja cirkulārs (gredzenveida) izskats, kā arī mazs audzēja izmērs (< 0,05). Pētījumā iekļautajiem KRV gadījumiem ar mucinozu un gredzenšūnu morfoloģiju bija raksturīgs liels audzēja izmērs un statistiski nozīmīga lokālo struktūru iesaiste. Pētījumā dominēja KRV gadījumi ar augstu lokālu izplatību: pT3 audzēji veidoja 49,6 %, pT4 35,6 % un pN + 40,5 % no pētāmās grupas. Audzējos ar augstu pT, pN un zemu diferenciācijas pakāpi tika novērota statistiski nozīmīgi plašāka nekrozes izplatība. Tika atrasta statistiski nozīmīga asociācija ar izteiktu lokālu iekaisumu un zemāku pT (p = 0,002), pN0 (p< 0,001), kā arī retākām lokālo struktūru invāzijām (p< 0,05). EMT (CD44, -katenīna, N-kadherīna un E-kadherīna), kā arī DNS labotājgēnu raksturojošo marķieru (MSH2, MSH6, PMS2 un MLH1) IHĶ ekspresija statistiski nozīmīgi neatšķīrās audzējos ar dažādas intensitātes peritumorozu iekaisumu un Krona slimībai līdzīgo limfocitāro reakciju. Tomēr, analizējot iekaisuma šūnu subpopulācijas, tika atrasta statistiski nozīmīga atšķirība E-kadherīna izteiktākā ekspresijā pie palielināta eozinofilo leikocītu daudzuma (p = 0,007). Zemāka N-kadherīna ekspresija bija raksturīga multifokāliem KRV gadījumiem. DNS labotājgēnu ekspresija statistiski ticami atšķīrās audzējos ar izmaiņām E-kadherīna un CD44 ekspresijā (p< 0,05). MLH1 proteīna zemāka ekspresija statistiski ticami saistījās ar zemāku neitrofilo leikocītu klātbūtni KRV (p = 0,02). Secinājumi. Audzējiem ar izteiktu peritumorozo iekaisumu ir raksturīga mazāka izplatība un lokālo struktūru invāzija. Krona slimībai līdzīgā limfocitārā reakcija neietekmē audzēja izplatību (pTN), tas netieši norāda uz šīs reakcijas neatkarīgu lomu kanceroģenēzē. Iekaisums, noteikts pēc Klintrupa–Makinena skalas (Klintrup-Makinen score), un Krona slimībai līdzīgā limfoīdā reakcija nav atkarīgi no EMT un cilmes šūnu diferenciācijas KRV. DNS labotājgēnu (MSH2, MSH6, PMS2 un MLH1) samazināta ekspresija KRV ir norāde par EMT procesu, kas potenciāli var ietekmēt terapijas izvēli KRV. MLH1 ekspresija KRV ietekmē neitrofilo leikocītu daudzumu peritumorozā iekaisumā, netieši norādot potenciālo DNS labotājgēnu nozīmi audzēja imunitātē. Šajā pētījumā raksturota iekaisuma, KRV morfoloģijas, EMT un DNS labotājgēnu mijiedarbība.Item Giant Myxopapillary Ependymoma with Multi-Site Neural Axis Metastases : A Rare Case with Suboptimal Outcome(2024) Balodis, Arturs; Ņeverčika, Viktorija; Zavertjajeva, Marija; Mikijanskis, Raimonds; Kalnina, Marika; Breikša-Vaivode, Austra; Briede, Inese; Department of Radiology; Department of PathologyObjective: Background: Case Report: Conclusions: Rare disease Myxopapillary ependymoma is a rare type of slow-growing tumor that mainly occurs in the spinal cord, particularly in the region of the conus medullaris and the cauda equina. It originates from the ependymal glial cells found in the filum terminale. We present a clinical case of a 44-year-old male patient who presented with symptoms of non-specific pain in the lower back persisting for the past 2 years. He did not report any specific neurological deficits or radicular symptoms. Unenhanced MRI of the lumbar spine showed a giant intradural, extramedullary, heterogenous, expansive tumor at the level L1-S4 with erosion of the sacral bone and invasion of presacral tissue. Based on its characteristic localization and growth pattern, suspicion arose for myxopapillary ependymoma. Biopsy confirmed the initial diagnosis. Partial resection of the tumor with laminectomy and laminoplasty was deemed necessary. Preoperative neural axis MRI showed contrast-enhancing lesions in the cerebellum and the cervical and thoracic spine; therefore, adjuvant radiation therapy was administered. Following the surgery, the patient experienced intermittent episodes of neurological deficits and required physiotherapy. Control MRI a year after the operation showed tumor growth and more metastases along the neural axis. Complete surgical excision of the tumor is the preferred treatment approach, but there is a risk of recurrence even after total excision, so radiotherapy is recommended to minimize the risk of recurrence. Prior to surgery, it is essential to conduct MRI/PET/CT of the head and spine to assess the possibility of metastases.Item Stemness, inflammation and epithelial–mesenchymal transition in colorectal carcinoma : The intricate network(2021-11-29) Briede, Inese; Balodis, Dainis; Gardovskis, Janis; Strumfa, Ilze; Department of Pathology; Department of SurgeryIn global cancer statistics, colorectal carcinoma (CRC) ranks third by incidence and second by mortality, causing 10.0% of new cancer cases and 9.4% of oncological deaths worldwide. Despite the development of screening programs and preventive measures, there are still high numbers of advanced cases. Multiple problems compromise the treatment of metastatic colorectal cancer, one of these being cancer stem cells—a minor fraction of pluripotent, self-renewing malignant cells capable of maintaining steady, low proliferation and exhibiting an intriguing arsenal of treatment resistance mechanisms. Currently, there is an increasing body of evidence for intricate associations between inflammation, epithelial–mesenchymal transition and cancer stem cells. In this review, we focus on inflammation and its role in CRC stemness development through epithelial–mesenchymal transition.Item Surgical Treatment of Hepatocellular Carcinoma with a Tumor Thrombus Invading the Right Atrium : A Case Report(2023-06-08) Veinberga, Laura; Meidrops, Kristians; Rumba, Roberts; Gedins, Marcis; Anufrijevs, Deniss; Vilmanis, Janis; Drizlionoka, Karina; Zellans, Edgars; Krustina, Inguna; Berzins, Juris; Briede, Inese; Sivins, Armands; Radzina, Maija; Stradins, Peteris; Ozolins, Arturs; Department of Surgery; Department of Pathology; Department of RadiologyUp to 3% of all hepatocellular carcinomas (HCCs) present with a tumor thrombus (TT) in the inferior vena cava (IVC) and right atrium (RA). Extensive growth of HCC into the IVC and the RA is associated with a particularly poor prognosis. This clinical condition is related to a high risk of sudden death due to pulmonary embolism or acute heart failure. Therefore, a technically challenging treatment undergoing hepatectomy and cavo-atrial thrombectomy is necessary. We report a 61-year-old man presenting with right subcostal pain, progressive weakness, and periodic shortness of breath for 3 months. He was diagnosed with advanced HCC with a TT extending from the right hepatic vein into the IVC and RA. A multidisciplinary meeting with cardiovascular and hepatobiliary surgeons, oncologists, cardiologists, anesthesiologists, and radiologists was held to determine the best treatment approach. Initially, the patient underwent right hemihepatectomy. As follows, the cardiovascular stage using cardiopulmonary bypass was successfully performed, removing the TT from the RA and ICV. In the early postoperative period, the patient remained stable and was discharged on the 8th postoperative day. A morphological examination revealed grade 2/3 HCC, a clear cell variant with microvascular and macrovascular invasion. Immunohistochemical staining was positive for HEP-1, CD10, whereas negative for S100. The morphological and immunohistochemical results corresponded to HCC. The treatment of such patients requires the cooperation of various specialties. Although the approach of the surgery is extremely complex including specific technical support, as well as high perioperative risks, the result offers favorable clinical outcomes.