Pattern Of Invasion Research Articles

SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.

Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear. The IL-17B/IL-17RB pathway is known to promote pancreatic cancer invasion and metastasis, yet the specific mechanisms underlying IL-17RB upregulation during invasion are poorly understood. In this study, we unveiled a multistep process for IL-17RB upregulation at the invasive margin, which occurs through direct communication between tumor cells and fibroblasts. Tumor ATP1A1 facilitates plasma membrane expression of SEMA7A, which binds to and induces IGFBP-3 secretion from fibroblasts. The resulting gradient of IGFBP-3 influences the direction and enhances IL-17RB expression to regulate SNAI2 in invasion. These findings highlight the importance of local tumor-fibroblast interactions in promoting cancer cell invasiveness, potentially leading to the development of new therapeutic strategies targeting this communication.

Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer.

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People's Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number-low (CNL), microsatellite instability-high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.

P1.06C.06 The Prognostic Impacts of Three Invasive Patterns in Pulmonary Peripheral Squamous Cell Carcinoma

P1.06C.06 The Prognostic Impacts of Three Invasive Patterns in Pulmonary Peripheral Squamous Cell Carcinoma

Conclusive evidence for the origin of the carcinoid component in strumal carcinoids and a new morphological pattern

Abstract Introduction/Objective There has been debate whether strumal carcinoids are carcinoids with areas resembling thyroid or arise from bonafide thyroid tissue in struma. While the thyroid nature has been proven by demonstrating positive TTF-1 in the struma component, evidence for the origin of the carcinoid component is sparse. Herein, we describe a case of strumal carcinoid and use a panel of markers to show definitive morphological and immunohistochemical evidence of the evolution of the neoplasm from struma ovarii to struma carcinoid, within the same lesion. We also report a unique component of a more sinister single cell pattern of invasion apart from the usual insular, trabecular, and mucinous patterns. Methods/Case Report A 40-year-old woman with an adnexal mass underwent bilateral salpingo- oophorectomy/hysterectomy. Microscopic analysis identified thyroid tissue consistent with struma ovarii, juxtaposed with a neuroendocrine neoplasm. The interface between the two showed strong PAX-8 and uniform TTF-1 staining in the struma but gradual loss of TTF-1 with retained/weak PAX-8 staining, moving away from the struma component and into the carcinoid. Additionally, a pattern of single cell invasion was identified, away from the main tumor and at the ovarian surface. These cells closely resemble luteinized ovarian stromal cells but are stained like the carcinoid tumor. Two months postoperatively, the patient had no evidence of recurrence or metastasis. Results (if a Case Study enter NA) NA Conclusion We have provided conclusive morphological and immunohistochemical evidence that strumal carcinoid develops from native neuroendocrine cells of thyroid tissue in struma ovarii. Specifically, retained/weak PAX-8 with interspersed TTF-1 in an adnexal carcinoid provides valuable insight when dealing with tumors of unknown etiology, strongly favoring an ovarian primary (specifically, from struma ovarii) and not metastasis from the gastrointestinal tract or other Mullerian tissue. Lastly, the single cell pattern of invasion that we elucidate here is something to be aware of in the context of metastases or frozen sections.

Non‐native invasive plants in tropical dry forests: a global review of presence, impacts, and management

Tropical dry forests (TDF) are among the most‐threatened terrestrial ecosystems, experiencing ongoing conversion to agricultural fields, pasture, and human settlements. Human disturbances are often precursors to invasion of ecosystems by non‐native species, but research on invasion patterns in tropical ecosystems is sparse, and there is no comprehensive synthesis of invasive species in TDF. We conducted a review of published scientific literature to catalog and synthesize information about invasion by non‐native plants in TDF ecosystems across the globe, drawing out patterns in the invasion of these ecosystems. We found that 130 invasive plant species were documented as present in TDF, but only 25 of these species were mentioned in three or more articles. Almost all 25 of these more‐studied invasive species—mostly pasture grasses, woody legumes, and climbers—have been intentionally cultivated for agricultural or ornamental purposes. Many of these plants are native to open‐canopy savanna or forest edge habitats and benefit from human‐altered disturbance regimes (burning, grazing, and fuelwood and timber harvesting) of TDF fragments within agricultural landscapes. Field studies show that management approaches incorporating invasive removal, native plantings, and reduction in agricultural disturbance (e.g. ungulate fencing and fire control) simultaneously are often the most successful at reducing invasive plant cover. However, management studies in TDF have focused on a limited number of invasive species, and most were conducted in India and Hawaii. Global differences in TDF soils, natural fire regimes, and historic and current land use by humans influence modern biogeographic patterns of invasion and the feasibility of restoration options.

Clinical experiences in precision treatment of giant plexiform neurofibromas of head, face, and neck

To summarize the treatment strategies and clinical experiences of 5 cases of giant plexiform neurofibromas (PNF) involving the head, face, and neck. Between April 2021 and May 2023, 5 patients with giant PNFs involving the head, face, and neck were treated, including 1 male and 4 females, aged 6-54 years (mean, 22.4 years). All tumors showed progressive enlargement, involving multiple regions such as the maxillofacial area, ear, and neck, significantly impacting facial appearance. Among them, 3 cases involved tumor infiltration into deep tissues, affecting development, while 4 cases were accompanied by hearing loss. Imaging studies revealed that all 5 tumors predominantly exhibited an invasive growth pattern, in which 2 and 1 also presenting superficial and displacing pattern, respectively. The surgical procedure followed a step-by-step precision treatment strategy based on aesthetic units, rather than simply aiming for maximal tumor resection in a single operation. Routine preoperative embolization of the tumor-feeding vessels was performed to reduce bleeding risk, followed by tumor resection combined with reconstructive surgery. All 5 patients underwent 1-3 preoperative embolization procedures, with no intraoperative hemorrhagic complications reported. Four patients required intraoperative blood transfusion. A total of 10 surgical procedures were performed across the 5 patients. One patient experienced early postoperative flap margin necrosis due to ligation for hemostasis; however, the incisions in the remaining patients healed without complications. All patients were followed up for a period ranging from 6 to 36 months, with a mean follow-up duration of 21.6 months. No significant tumor recurrence was observed during the follow-up period. For patients with giant PNF involving the head, face, and neck, precision treatment strategy can effectively control surgical risks and improve the standard of aesthetic reconstruction. This approach enhances overall treatment outcomes by minimizing complications and optimizing functional and cosmetic results.

Habitat-based CT radiomics enhances the ability to predict spread through air spaces in stage T1 invasive lung adenocarcinoma.

Spread through air spaces (STAS) represents a novel invasive pattern in lung adenocarcinoma (LUAD) and is a risk factor for poor prognosis in stage T1 LUAD. This study aims to develop and validate a CT habitat imaging analysis model for predicting STAS in stage T1 invasive LUAD. We retrospectively analyzed 217 patients with preoperative stage T1 invasive LUAD (115 STAS-positive and 102 STAS-negative cases, including 151 in the train set and 66 in the test set). Semi-automatic segmentation was performed on the regions of interest (ROIs) in all CT images, with an automatic 3mm expansion around the tumor, considering the intratumoral and peritumoral 3mm area. This area was divided into three sub-regions via K-means clustering, and 1197 radiomic features were extracted from each sub-region and the overall combined region. After dimension reduction through the Mann-Whitney U test, Pearson correlation analysis, and least absolute shrinkage and selection operator(LASSO), the best features for each sub-region and overall were selected. Models were then built using the selected radiomic features through the Adaptive Boosting (AdaBoost) and Multilayer Perceptron (MLP) classifiers. Four different models were established based on different sub-regions and the overall features. The performance of these models was evaluated through receiver operating characteristic curves (AUC) under the DeLong test, calibration curves via the Hosmer-Lemeshow test, and decision curve analysis to assess the performance of these features. In this study, we evaluated the predictive performance of AdaBoost and MLP classifiers on rad feature models across various subregions and the overall dataset. In the test set, the AdaBoost classifier achieved a maximum AUC of 0.871 in Habitat 3, whereas the MLP classifier demonstrated slightly superior performance with an AUC of 0.879. Both classifiers exhibited high efficiency in habitat 3, with the MLP algorithm showing enhanced model performance. CT habitat imaging analysis for the preoperative prediction of STAS in stage T1 invasive LUAD shows satisfactory diagnostic performance, with the habitat3 model exhibiting the highest efficacy, reflecting tumor heterogeneity.

Stereologic consequences of iatrogenic collapse: The morphology of adenocarcinoma in situ overlaps with invasive patterns. Proposal for a necessary modified classification of pulmonary adenocarcinomas

Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma in-situ (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up.The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information.The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation.The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months.With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.

HMGA2-positive salivary gland neoplasms with prominent trabecular/canalicular morphology: a focus on carcinomas arising within this phenotype.

Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with HMGA2 fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context. A retro- and prospective review (2013-2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty-one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next-generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma-like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well-demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S-100, and SOX-10 and variable expression of p63 but negative p40. HMGA2 alterations were detected in 16 of 18 cases (89%). Follow-up was available on two carcinomas, with one being locally recurrent. While most HMGA2-positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion.

Eimeria tenella rhoptry neck protein 2 plays a key role in the process of invading the host intestinal epithelium

The Apicomplexa parasitic phylum rhoptry neck protein 2 (RON2) plays a key role in the process of invading host cells. Eimeria tenella, an intracellular protozoan shares a similar conserved invasion pattern. However, whether E. tenella RON2 participates in the process of invading the host intestinal epithelium is poorly understood. In this study, the sequence of EtRON2 was analyzed and expressed. The expression of the truncated extracellular N-terminal fragment of EtRON2 (403–700 aa, designated EtRON2403–700) with a molecular mass of 38.3 kDa. EtRON2 in the sporozoite protein was detected at 151.4 kDa by rabbit anti-rEtRON2403–700 antibody. Immunofluorescence results showed that EtRON2 was mainly localized to the nucleus and apex of the E. tenella sporozoite. qPCR results showed that the highest expression level of EtRON2 was detected in sporulated oocysts compared with other developmental stages of E. tenella. In vitro invasion inhibition assays showed that the capacity of sporozoites to invade DF-1 cells was significantly inhibited after pretreatment with the rabbit anti-rEtRON2403–700 antibody. Silencing the EtRON2 gene by RNA interference (RNAi) significantly inhibited EtRON2 expression and significantly reduced the invasion of DF-1 cells by sporozoites. In vivo experiments revealed a significant decrease parasite burden and oocyst outputs in chicks after infection with EtRON2 gene-silenced sporozoites by cloacal inoculation. Recombinant EtRON2403–700 (rEtRON2403–700) immunizes chicks effectively against E. tenella infection by inducing humoral immunity and upregulating IFN-γ and CD8+ T lymphocytes. Furthermore, chicks exhibited increased relative weight gain rates, lower cecum lesion scores, and reduced oocyst outputs during the E. tenella challenge. H&E staining showed that the cecum tissue of chicks immunized with rEtRON2403–700 showed relatively mild histopathological changes. In conclusion, the results of this study demonstrated that EtRON2 plays a key role in E. tenella invasion of the host intestinal epithelium and provides a potential target for vaccines against E. tenella infection.

TEMPORARY REMOVAL: Understanding gaps in early detection of and rapid response to invasive species in the United States: A literature review and bibliometric analysis

While concepts regarding invasive species establishment patterns and eradication possibilities have long been a topic of invasion biology, the specific terminology referring to early detection of and rapid response to (EDRR) invasive species emerged in scientific literature during the early 2000s. Since then, the EDRR approach has expanded to include a suite of detection, planning, and management tools. By conducting a systematic literature review, we attempt to characterize the field of EDRR in the United States and its territories as reflected by publication records. Specifically, we assessed publication data such as the number of publications per year, the most common journals where papers were published, and the relationship between author's keywords for studies focusing on aquatic and terrestrial habitats. For publications that used invasive species occurrence or abundance data (whether collected for the purposes of the respective publication or acquired from another data source), we manually vetted additional information such as focal taxa, data collection years and locations, sources of other data used, and whether data or code were deposited in open access formats. We also conducted network analyses for the author institutions that coauthored papers together most frequently and for the references most cited by EDRR publications. Overall, we found that silos existed in terms of which author institutions worked together, which existing literature was cited, and which topics were frequently explored. We also found evidence of substantial gaps in data access and use. For example, although a wide variety of data sources for invasive species occurrences are available, these sources were seldom cited by published literature, and newly collected data was not often deposited into invasive species databases or other open-source data repositories. Considering the continued advocation for a centralized national EDRR information system, our study suggests that facilitating access to data, decision support tools, and other informational resources represents a key opportunity for improving EDRR capabilities.

Significance of radiation therapy in frontal glioblastoma patients and exploration of optimal treatment modality: a real-world multiple-center study based on propensity score matching.

Glioblastoma (GBM) exhibits diffuse and invasive growth patterns, with a 5-year overall survival (OS) rate of 5-10%. In addition, approximately 40 percent of GBMs are localized in the frontal lobe, a region closely linked to essential life functions including cognition, so that it cannot be completely eradicated through surgical intervention, leading to very poor prognosis. Postoperative therapy is an essential treatment modality. The aim of this study is to explain the possible role of radiation therapy (RT) in the treatment of frontal GBM, providing more evidence for clinical application. In the study, patient information pertaining to frontal GBM patients was collected from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018 with 9,904 patients deemed appropriate for inclusion in this study. A 1:2 propensity score matching analysis was conducted to balance the non-radiotherapy and radiotherapy group. This study is a retrospective study. Before matching, the median OS, tumor specific survival (TSS) and hazard ratio (HR) were 3 months, 3 months and 4.408 [95% confidence interval (CI): 3.762-4.535, P<0.001] in the non-RT group compared to those of 13 months, 14 months and 2.463 (95% CI: 2.247-2.936, P<0.001) in the RT group. After matching, the median OS, TSS and HR were 3 months, 4 months and 1.433 (95% CI: 1.387-1.692, P<0.001) in the non-RT group compared to those of 8 months, 8 months and 1.427 (95% CI: 1.374-1.682, P<0.001) in the RT group. Radiotherapy is an important local therapy, which can significantly improve the tumor-specific survival and OS of frontal GBM patients. With the arrival of the era of precision radiotherapy, the continuous progress of radiotherapy technology may bring more benefits to frontal GBM patients.

Multiple origins of freshwater invasion and parental care reflecting ancient vicariances in the bivalve family Cyrenidae (Mollusca)

Habitat transitions in living organisms are key innovations often coupled with species diversification after their successful adaptation to new environment. The Cyrenidae is among the most well-known heterodont bivalve groups that have successfully invaded freshwater systems from brackish water environments and display diverse lineage-specific developmental modes. Phylogenetic and molecular clock-based divergence time analyses using 12 complete mitochondrial genome sequences suggest that Cyrenidae species independently colonized freshwater habitats during three distinct spatial and geological periods: one from the American continents approximately in the Early Jurassic and the two others from Australasian/East Asian continents in the Early/Middle Cretaceous and the Paleogene-Neogene boundary, respectively. This study provides significant insight into the temporal and spatial patterns of multiple freshwater invasions, aligning with ancient vicariance events inferred from different geological timelines of plate tectonics. Additionally, mitogenome phylogeny confirms the earlier hypothesis of the repeated parallel evolution of parental care system within this bivalve group.

Novel Nomogram for Prediction of Lymph Node Metastases from Buccal Mucosa Squamous Carcinoma Using Histological Parameters

Objective The aim of the study was to construct a nomogram that is easily reproducible, accurate, and cost-effective in predicting cervical lymph nodal metastasis in buccal mucosa cancer. Methodology Patients who underwent radical resection of a primary tumor of the buccal mucosa with neck dissection were enrolled. Clinical characteristics independently associated with lymph nodal metastasis in multivariate analyses were adopted to build the model. Results Patients who underwent surgery (January 2021–December 2021) were included as the model development cohort (n = 127). Depth of invasion, perineural invasion, lymphovascular invasion, and the worst pattern of invasion were independent predictors of lymph nodal metastasis. The nomogram model based on these four predictors showed good discrimination accuracy in percentage prediction of lymph nodal metastasis. Conclusion This study proposes a simple predictive model for the risk of nodal metastasis in buccal mucosa squamous cell cancer. The study has strength that, it is based on a large sample, proposed model being simple size, and based on parameters empirically supported as well as established in literature, easy to use in routine clinical practice, and cost-effective.

Neoteric Predictors for Lymph Node Metastasis in Early Oral Squamous Cell Carcinoma: Tumor Budding and Worst Pattern of Invasion

Neoteric Predictors for Lymph Node Metastasis in Early Oral Squamous Cell Carcinoma: Tumor Budding and Worst Pattern of Invasion

Single-cell profiling uncovers proliferative cells as key determinants of survival outcomes in lower-grade glioma patients

Lower-grade gliomas (LGGs), despite their generally indolent clinical course, are characterized by invasive growth patterns and genetic heterogeneity, which can lead to malignant transformation, underscoring the need for improved prognostic markers and therapeutic strategies. This study utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to identify a novel cell type, referred to as "Prol," characterized by increased proliferation and linked to a poor prognosis in patients with LGG, particularly under the context of immunotherapy interventions. A signature, termed the Prol signature, was constructed based on marker genes specific to the Prol cell type, utilizing an artificial intelligence (AI) network that integrates traditional regression, machine learning, and deep learning algorithms. This signature demonstrated enhanced predictive accuracy for LGG prognosis compared to existing models and showed pan-cancer prognostic potential. The mRNA expression of the key gene PTTG1 from the Prol signature was further validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings not only provide novel insights into the molecular and cellular mechanisms of LGG but also offer a promising avenue for the development of targeted biomarkers and therapeutic interventions.

Local Invasion Patterns Characterized by SARIFA and Tumor Budding Differ and Have Distinct Prognostic Significance in Esophageal Adenocarcinoma and Squamous Cell Carcinoma.

Both esophageal squamous cell carcinoma (ESQCC) and adenocarcinoma (EAC) are known to have poor prognosis. We aimed to investigate the invasion front areas of 57 ESQCC and 43 EAC cases to find histological signs of metastatic progression. Tumor cell clusters with different cell counts, including tumor buds (TBs) and poorly differentiated clusters (PDCs), were assessed. The presence of the recently described Stroma AReactive Invasion Front Area (SARIFA) phenomenon, which defines a direct contact between tumor cells and adipocytes, was more frequently observed in EAC than in ESQCC (p = 0.004). In adenocarcinomas, a higher prevalence of SARIFA was observed in tumors with a higher number of small clusters (TBs and small PDCs; p < 0.001); furthermore, both the high number of TBs (p = 0.016) and the presence of SARIFA (p = 0.001) correlated with a higher pT stage. SARIFA positivity in EAC (p = 0.011) and high TB in ESQCC (p = 0.0006) were found to be independent prognostic factors for lymph node metastases. Moreover, in ESQCC, the higher absolute number of both TBs and PDCs was associated with shorter overall survival (p = 0.0269 and p = 0.0377, respectively). Our results suggest that the histological subtypes of esophageal cancer behave differently, namely, that different features of the invasion front are of prognostic significance.

New histological risk grading system for prediction of lymph node metastasis in patients with penile cancer

AbstractInguinal lymph node surgery is a standard treatment for penile cancer patients with intermediate or high risk for lymph node metastasis (LNM) according to European Association of Urology (EAU) risk grading. We are proposing a more objective histological prognostic grading system for inguinal LNM in these patients. We assessed worst pattern of invasion, lymphocytic host response, lymphovascular invasion, and perineural invasion in a population-based cohort of 306 penile cancer patients. Patients were classified into low, intermediate, and high risk for inguinal LNM. There was a significant association both between risk groups and pT stage (p &lt; 0.001) and between risk groups and LNM. Univariate logistic regression showed 25.43 times higher odds of LNM for patients in the intermediate risk group compared with the low risk group (odds ratio (OR) 25.43; 95% confidence interval (CI): 5.94–108.97) and a 177.13 times higher odds in the high risk group compared to the low risk group (OR 177.13; 95% CI: 40.09–782.51). When comparing our histological risk grading with the EAU grading, we found a higher sensitivity, of 51.28% (95% CI: 45.68–56.88) versus 37.09% (95% CI: 31.68–42.50), as well as a higher area under the curve (0.86; 95% CI: 0.81–0.89; versus 0.65; 95% CI: 0.58–0.71) with our grading system. While our grading classified 111 patients as low risk, only 31 were considered low risk for LNM according to the EAU risk classification. The new histological risk grading system shows a higher sensitivity and includes a higher number of patients in the low risk group in whom lymph node surgery could be avoided, reducing morbidity and costs.

Lysosome-Associated Membrane Protein-3 (LAMP3) Expression in Oral Squamous Cell Carcinoma and Its Relationship With Clinicopathological Parameters: A Cross-Sectional Study.

Background Oral squamous cell carcinoma (OSCC) accounts for the majority of oral cancers globally. It is characterized by metastasis, poor prognosis, high recurrence rate, and poor five-year survival rate due to late detection or diagnosis at an advanced stage. Novel biomarkers that can predict the prognosis of patients with OSCC are needed to improve survival. Lysosome-associated membrane protein-3 (LAMP3) glycoprotein, a member of the LAMP protein family, is a molecular marker for mature dendritic cells. LAMP3 expression has been correlated with unfavorable prognosis in patients with various cancers. Few studies have examined the relationship between LAMP3 and clinicopathological parameters in OSCC. This study aims to analyze the immunohistochemical expression of LAMP3 in OSCC and its relationship with clinicopathological characteristics. Methodology In this study, 75 formalin-fixed, paraffin-embedded samples of cases diagnosed with primary OSCC were obtained and immunostained with LAMP3 antibody. Its expression was compared with clinicopathological parameters such as age, sex, tobacco and alcohol consumption habits, differentiation, TNM staging, tumor location, lymph node metastasis, lymphovascular invasion, perineural invasion, and pattern of invasion. Results Higher LAMP3 expression was highly significantly associated with the TNM stage (p = 0.001). High expression of LAMP3 was significantly associated with T stage (p = 0.002) and lymph node metastasis (p = 0.002). All poorly differentiated OSCC cases (n = 2, 100%) showed a high expression of LAMP3. Conclusions High LAMP3 expression and its significant association with TNM stage, T stage, and lymph node metastasis suggest a potential role for LAMP3 in OSCC carcinogenesis. High LAMP3 expression in poorly differentiated OSCC might indicate that it plays a pivotal role in oncogenic cell transformation. Our results indicate that LAMP3 may be a predictive marker for poor prognosis in OSCC.

Improved Risk Prediction in Human Papillomavirus-Associated Endocervical Adenocarcinoma Through Assessment of Binary Silva Pattern-based Classification: An International Multicenter Retrospective Observational Study Led by the International Society of Gynecological Pathologists (ISGyP).

Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations.