Histology and histopathology最新文献

{"title":"Histopathological aspects of usual interstitial pneumonia in patients with systemic connective tissue diseases.","authors":"Mária Makovická, Barbora Durcová, Adela Vrbenská, Peter Makovický, Patricie Michalčová, Klaudia Kráľová, Jozef Muri","doi":"10.14670/HH-18-777","DOIUrl":"10.14670/HH-18-777","url":null,"abstract":"<p><p>Five cases of patients with systemic connective tissue diseases (CTD) who developed connective tissue disease-associated interstitial lung disease (CTD-ILD) with progressive pulmonary fibrosis (PPF) are reported here. Unspecified ILD was diagnosed using high-resolution computed tomography (HRCT). Histologically, all cases were usual interstitial pneumonia (UIP) with findings of advanced (3/5) to diffuse (2/5) fibrosis, with a partially (4/5) to completely (1/5) formed image of a honeycomb lung. The fibrosis itself spread subpleurally and periseptally to more central parts (2/5) of the lung, around the alveolar ducts (2/5), or even without predisposition (1/5). Simultaneously, there was architectural reconstruction based on the mutual fusion of fibrosis without compression of the surrounding lung parenchyma (1/5), or with its compression (4/5). The whole process was accompanied by multifocal (1/5), dispersed (2/5), or organized inflammation in aggregates and lymphoid follicles (2/5). As a result of continuous fibroproduction and maturation of the connective tissue, the alveolar septa thickened, delimiting groups of alveoli that merged into air bullae. Few indistinctly visible (2/5), few clearly visible (1/5), multiple indistinctly visible (1/5), and multiple clearly visible (1/5) fibroblastic foci were present. Among the concomitant changes, areas of emphysema, bronchioloectasia, and bronchiectasis, as well as bronchial and vessel wall hypertrophy, and mucostasis in the alveoli and edema were observed. The differences in the histological appearance of usual interstitial pneumonia associated with systemic connective tissue diseases (CTD-UIP) versus the pattern associated with idiopathic pulmonary fibrosis (IPF-UIP) are discussed here. The main differences lie in spreading lung fibrosis, architectural lung remodeling, fibroblastic foci, and inflammatory infiltrates.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"49-56"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous specimen cooling during slicing and thickness measurement contributes to improved accuracy in image analysis of pathologic specimens.","authors":"Masanao Saio, Raia Kushibiki, Yuki Kanehira, Akifumi Ishizawa, Yuka Abe, Sayaka Kobayashi, Yoshimi Nishijima","doi":"10.14670/HH-18-751","DOIUrl":"10.14670/HH-18-751","url":null,"abstract":"<p><p>We measured section thickness (ST) after slicing using a film thickness meter and investigated the relationship between ST and the percent area of positive staining using computer-assisted image analysis.</p><p><strong>Methods: </strong>Sections were prepared from a paraffin-only block and formalin-fixed paraffin-embedded (FFPE) blocks containing fish sausage and human liver specimens. The ST was compared between the sections prepared with cooling using an ice pack (IP) or a continuous cooling device (CCD) paired with a sliding microtome set at an ST of 4 µm. The sections were stained with eosin or aniline blue, and the association between the percent area of positive staining and ST was determined using computer-aided analysis of images captured with a whole slide scanner.</p><p><strong>Results: </strong>The average STs of the paraffin-only block sections measured by four practitioners were 5.01-5.41 and 4.09-4.33 µm in samples prepared using an IP and a CCD, respectively. Therefore, subsequent analyses included sections prepared using the CCD. The ST of the tissue surface was significantly thinner than that of the paraffin surrounding the tissue section. Furthermore, the percent areas of positive staining for eosin and aniline blue were significantly correlated with ST in both the fish sausage and liver sections. The analysis of the ST and percent area of positive staining in 60 sections of the same block, which were categorized into quantiles based on ST, revealed a significant difference in the percent area of positive staining between the thicker and thinner sections.</p><p><strong>Discussion: </strong>Specimen sectioning should be performed with a CCD, ST should be measured before the staining of pathologic specimens prepared for quantitative analysis, and histologic examination should be performed using specimens with uniform ST.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"31-38"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristic abnormal expression of galectin-3 in serrated colon lesions and its pathological significance.","authors":"Zhiyi Zhou, Dandan Huang, Ying Cai, Shudong Yang, Nanxing Jiang, Qiang Zhan","doi":"10.14670/HH-18-759","DOIUrl":"10.14670/HH-18-759","url":null,"abstract":"<p><p>Serrated lesions are precursors of some colon cancers. The expression of galectin-3 has been reported to be involved in <i>BRAF</i> and <i>KRAS</i> mutations (the key pathogenic drivers of serrated lesions). This study aimed to investigate the expression intensity and subcellular localization of galectin-3 in serrated colon lesions by immunohistochemistry. The results demonstrated that, regarding expression intensity, galectin-3 expression in serrated colon lesions was significantly upregulated; regarding subcellular localization, the membrane expression of hyperplastic polyps/ sessile serrated lesions (HP/SSL) was weakened, the structure was disorganized and that of traditional serrated adenoma (TSA) was significantly weakened or disappeared, and the nuclear expression of both was positive; in the dysplasia of SSL (SSL-D) and TSA (TSA-HD), galectin-3 expression intensity remained high, and was weakened or disappeared in some nuclei, the expression disorder of the SSL-D cell membrane was reduced, the polarity of the cell was restored, weak expression appeared in the local cell membrane of TSA-HD, and the \"serrated\" structure of both was reduced or disappeared and seemed to revert more to that seen in common adenomas. In summary, abnormal galectin-3 expression occurs in the early stages of serrated lesions, its expression is characteristic, the dynamic changes in galectin-3 expression are closely related to the histopathological changes and progression of serrated lesions, and further accumulated molecular alterations contribute to this process.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"67-72"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclin-dependent kinase 5 as a potential therapeutic target to alleviate high glucose-induced podocyte apoptosis and hyperglycemia-induced renal injury in mice.","authors":"Li Zhao, Wenjuan Gu, Wenfang He, Kaibi Yang, Nan Yang, Yanqing Jia","doi":"10.14670/HH-18-764","DOIUrl":"10.14670/HH-18-764","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia is a risk factor for impaired renal function, including cellular metabolic disturbance, apoptosis, inflammation, and histologic lesion. This study aims to investigate the potential therapeutic targeting of cyclin-dependent kinase 5 (Cdk5) in hyperglycemia-induced podocyte dysfunction and renal damage.</p><p><strong>Methods: </strong>Cell viability and apoptosis of podocytes were assessed through CCK-8 and TUNEL staining, respectively, following exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with Cdk5 inhibitors (trans-resveratrol, myricetin, salvianolic acid A, and BML-259). Diabetic mice were established by intraperitoneal injection of freshly streptozotocin (STZ), which was given at a dose of 35 mg/kg in five successive injections. Additionally, histochemical staining was employed to evaluate the morphologic lesion of the kidney.</p><p><strong>Results: </strong>Cdk5 was found to be activated by HG stimulation both <i>in vitro</i> and <i>in vivo</i>. Notably, the inhibition of Cdk5 effectively mitigated the podocyte dysfunction induced by HG, including growth inhibition, membrane damage, and apoptosis. The compounds Trans-resveratrol, myricetin, salvianolic acid A, and BML-259 exhibited low binding energy values of -8.032 kcal/mol, -8.693 kcal/mol, -8.743 kcal/mol, and -10.952 kcal/mol, respectively, indicating strong and stable binding affinity between these candidates and Cdk5. The results of <i>in vivo</i> experimental analysis demonstrate that Cdk5 inhibitors, namely trans-resveratrol, myricetin, salvianolic acid A, and BML-259, confer protection against tubular and glomerular lesions induced by hyperglycemia.</p><p><strong>Conclusion: </strong>Both myricetin and BML-259 exhibit comparable protective effects on renal injury by inhibiting Cdk5.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"101-112"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0070440 mediates the prognosis and progress of human prostate cancer.","authors":"Min Huang, Junming Zhang, Wentao Luo, Tingting Li, Qiong Song, Lixiao Zhang, Min Cao, Shuang Li","doi":"10.14670/HH-18-765","DOIUrl":"10.14670/HH-18-765","url":null,"abstract":"<p><strong>Background: </strong>This study was designed to explore whether hsa_circ_0070440 was dysregulated in prostate cancer (PCa), and assess the effects of hsa_circ_0070440 alteration on PCa prognosis and cell function.</p><p><strong>Methods: </strong>The expression levels of hsa_circ_0070440 were assessed in PCa tissues and cell lines. After the classification of patients with PCa based on mean hsa_circ_0070440 level in 138 cases, Chi-square test and survival analyses (Kaplan-Meier method and multivariable Cox proportional hazards analysis) were performed to assess the predictive value of hsa_circ_0070440 in treatment failure (TTF), time to PSA progression (TTPP) and overall survival time. To examine the function of hsa_circ_0070440 in PCa cells, 22Rv1 and C4-2B cells were used for CCK-8 proliferation and Transwell migration assays. Hsa_circ_0070440- and TXNDC5-specific bindings with miR-382/383-5p were validated by bioinformatic analysis and luciferase gene reporter assay.</p><p><strong>Results: </strong>An increased expression of hsa_circ_0070440 was found in PCA tissues and cell lines, associated with clinical T stage (<i>p</i>=0.021) and lymph node metastasis. Hsa_circ_0070440 predicted poor overall survival, TTPP, and TTF, acting as independent prognostic factors for overall survival, TTPP, and TTF in patients with PCa. Knockdown of hsa_circ_0070440 inhibited cell proliferation and migration <i>in vitro</i>. Furthermore, hsa_circ_0070440 could sponge miR-382/383-5p. <i>TXNDC5</i> was a common target gene for miR-382/383-5p in PCa cells.</p><p><strong>Conclusion: </strong>This study demonstrated that hsa_circ_0070440 can predict the prognosis of PCa patients. Hsa_circ_0070440 can facilitate the proliferation and migration of PCa cells, possibly by sponging miR-382/383-5p.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"113-121"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIB1 facilitates the proliferation and migration of ovarian cancer cells by inducing EMT progression.","authors":"Guangyan Shi, Kristian Holgersson, Zhen Xin, Laszlo Szekely, Qiqiao Du, Xu Jing","doi":"10.14670/HH-18-868","DOIUrl":"https://doi.org/10.14670/HH-18-868","url":null,"abstract":"<p><strong>Aim: </strong>Ovarian cancer (OC) is a fatal female malignant tumor that severely impacts the health of women worldwide. Due to the lack of diagnostic biomarkers, 70% of OC patients are considered in the advanced stage at the first diagnosis. Exploring novel biomarkers for OC diagnosis has become an urgent clinical need to address. TRIB1 is a newly discovered oncogene in several malignant tumors, including acute myeloid leukemia, prostate cancer, and breast cancer. However, the biological function of TRIB1 in OC remains uncertain and, therefore, was explored in the present study.</p><p><strong>Methods: </strong>Levels of TRIB1 in OC and normal tissues were evaluated in the GEPIA database. TRIB1-KD was constructed in ES-2 cells and TRIB1-OE was constructed in OVCAR3 cells using a siRNA and OE vector, respectively. The proliferation ability was determined using the CCK-8 and clone formation assays. The migration ability was detected using the wound healing and Transwell assays. The expression of epithelial-mesenchymal transition (EMT) biomarkers was determined using western blotting.</p><p><strong>Results: </strong>TRIB1 was markedly upregulated in OC tissues compared with normal ovarian tissues in the GEPIA database. The TRIB1 level was slightly altered among ES-2, CAOV3, and SKOV3 cells, with the highest expression in ES-2 cells, which was greatly reduced in OVCAR3 cells. In TRIB1-KD ES-2 cells, a remarkably reduced proliferation ability was observed with the CCK-8 and clone formation assays, accompanied by a reduction in migration distance in the Wound healing assay and the number of migrated cells in the Transwell assay. In contrast, in TRIB1-OE OVCAR3 cells, increased proliferation ability was observed, accompanied by increased migration distance and number of migrated cells. Furthermore, EMT progression was markedly repressed in TRIB1-KD ES-2 cells and remarkably enhanced in TRIB1-OE OVCAR3 cells.</p><p><strong>Conclusion: </strong>TRIB1 facilitated the proliferation and migration of OC cells by enhancing EMT progression.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18868"},"PeriodicalIF":2.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the impact of <i>Momordica Charantia</i> on the testis of cisplatin-treated albino rats: Biochemical, histopathological, and ultrastructural study.","authors":"Fatma Mohsen Shalaby, Amany Omar Elrefaie, Safaa Zaky Arafa, Kandil Abd Attia","doi":"10.14670/HH-18-867","DOIUrl":"10.14670/HH-18-867","url":null,"abstract":"<p><p>Cisplatin is an antineoplastic drug that exhibits toxicity dependent on dosage and has adverse reproductive effects. <i>Momordica charantia</i> (Bitter melon) is a natural vegetable plant; its active ingredients possess antioxidant, apoptotic, antiproliferative, hypoglycemic, and other therapeutic properties. This study evaluates the effect of the administration of bitter melon extract, cisplatin, and cisplatin/bitter melon cotreatment on liver and kidney functions, serum and testicular oxidative status, testis histology, and sperm parameters. Adult male Wistar rats were randomly divided into four groups: Group I (Control) received normal saline, Group II received oral bitter melon extract (300 mg/kg), Group III received cisplatin (2.5 mg/kg), and Group IV received the same doses of cisplatin and bitter melon, for six successive weeks, daily. Our results showed that bitter melon extract stimulates antioxidant enzymes and has anti-lipid peroxidation properties through the significantly increased plasma levels of glutathione and significantly decreased testicular malondialdehyde. The cisplatin-treated group showed oxidative stress indicated by the significant decrease of catalase, glutathione, and superoxide dismutase levels and a significant increase in malondialdehyde levels in both serum and testis compared with the control group. In the cisplatin/bitter melon-cotreated group, there was a significant increase in superoxide dismutase and a significant decrease in malondialdehyde in both serum and testis compared with cisplatin-treated rats. The bitter melon alone or with cisplatin cotreatment resulted in reduced gonadosomatic index, sperm count, motility, and viability. These results were confirmed by histopathological examinations, apoptosis assay using flow cytometry, and immunohistochemical staining for proliferating cell nuclear antigen. In conclusion, the administration of bitter melon extract alone or in combination with cisplatin led to testicular structure disturbances and showed an anti-spermatogenic effect. These findings are likely due to a combination of inhibited cellular proliferation, increased cell death, minor decrease in testosterone levels, and localized oxidative stress that outweigh the antioxidant benefits of bitter melon extract.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18867"},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential protective effects of curcumin on the diabetic ovary: Experimental and molecular approaches.","authors":"Kıymet Kübra Tufekci, Gamze Altun, Maulilio John Kipanyula, Süleyman Kaplan","doi":"10.14670/HH-18-866","DOIUrl":"https://doi.org/10.14670/HH-18-866","url":null,"abstract":"<p><p>Diabetes mellitus (DM) causes numerous systemic diseases in animals and humans. This may also lead to reproductive problems among individuals of reproductive age. Detrimental effects such as apoptosis in ovarian granulosa cells, degradation of communication proteins, decreased oocyte quality, delayed meiotic maturation, and atrophy are among the increasing evidence that chronic hyperglycemia causes reproductive problems. Numerous studies have reported that the antidiabetic properties of the antioxidant curcumin may be due to its inhibition of oxidative stress, inflammation, and insulin resistance. There are also data indicating that curcumin reduces the risk of DM and its associated symptoms. This review discusses the protective or curative properties of curcumin in the treatment of DM-related problems in the ovary and seeks to elucidate potential underlying mechanisms. While the use of curcumin as a supportive/therapeutic agent has been introduced for the reduction of reproductive problems that may be caused by uncontrolled DM, more studies on this subject are needed.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18866"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related differences in the morphology of rectal mucosa-associated lymphoid tissues in C57BL/6NCrSlc mice.","authors":"Md Zahir Uddin Rubel, Md Abdul Masum, Takashi Namba, Masaya Hiraishi, Yasuhiro Kon, Osamu Ichii","doi":"10.14670/HH-18-865","DOIUrl":"10.14670/HH-18-865","url":null,"abstract":"<p><p>Sex hormones regulate gut function and mucosal immunity; however, their specific effects on the mucosa-associated lymphoid tissue (MALT) in the rectum of mammals remain unclear. Here, we aimed to investigate the influence of sex on MALT in the rectum of mammals by focusing on the rectal mucosa-associated lymphoid tissues (RMALTs) of C57BL/6NCrSIc mice. Histological analysis revealed that RMALTs were predominantly located in the lamina propria and submucosa of the rectal mucosa, with a significant sex-related difference in the distance from the anorectal junction to the first appearance of the RMALT. Despite similar RMALT numbers, females exhibited significantly larger RMALTs than males. Immunostaining revealed the presence of various immune cells, including T cells, B cells, macrophages, proliferative immune cells, lymphatic vessels, and high endothelial venules (HEVs), in RMALTs. Compared with males, females showed elevated T cell, helper T cell, and cytotoxic T-cell gene expression levels, along with high percentages of specific T-cell subsets. The factors influencing RMALT development, such as the presence of HEVs, C-X-C motif chemokine ligand 13 expression, and RMALT-containing cell proliferation, were also explored. Overall, this study revealed the detailed attributes of RMALTs, their immune cell composition, and their determinants in male and female mice, providing insights into the sex-specific characteristics of the rectal mucosal immune system.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18865"},"PeriodicalIF":2.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Value of the combination of intraepithelial tumor-infiltrating lymphocyte density and the heterogeneity of density as a prognostic marker in stage III colorectal cancers.","authors":"Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Hye Seung Lee, Gyeong Hoon Kang","doi":"10.14670/HH-18-864","DOIUrl":"https://doi.org/10.14670/HH-18-864","url":null,"abstract":"<p><p>Tumor-infiltrating lymphocyte (TIL) density is both a prognostic and a predictive factor in colorectal cancer (CRC). Whether the heterogeneity of TIL density across the tumor plays an important role in the clinical outcome of CRC is not well known. Adjuvant chemotherapy-treated patients with stage III CRC were analyzed for survival according to TIL density and density heterogeneity, which were determined on CD8-immunostained slides using a machine learning method and by calculating the Simpson evenness index, respectively. High heterogeneity of the intraepithelial TIL density was found to be an independent prognostic factor, with a hazard ratio of 1.970 (1.207-3.215) in the multivariate analysis of recurrence-free survival. High heterogeneity was closely associated with a high T category, venous invasion, perineural invasion, and <i>KRAS</i> mutation. The combination of both intraepithelial TIL density and density heterogeneity was significantly associated with the prognosis of patients: low TIL density/high TIL heterogeneity showed hazard ratios of 3.284 (1.639-6.578) and 4.176 (1.713-10.178) in the discovery and validation cohorts, respectively. Our findings suggest that the heterogeneity status of intraepithelial TIL density might help delineate patients with better vs. worse survival when combined with intraepithelial TIL density.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18864"},"PeriodicalIF":2.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}