Corrigendum: Case Report: Surgical treatment of a primary giant epithelioid hemangioendothelioma of the spine with total en-bloc spondylectomy.

[This corrects the article DOI: 10.3389/fonc.2023.1109643.].

Correlation of NPDC1 Expression and Perineural Invasion Status with Clinicopathological Features in Patients with Colon Cancer.

Background: Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to well-known hematogenous and lymphatic metastasis, perineural invasion (PNI) has emerged as a significant mode of distant metastasis in colon tumors. PNI is closely associated with oncologic pain in advanced cancer patients, but the underlying mechanisms and associated biomarkers, which might be the novel therapeutic targets, remain poorly understood. Methods: In this study, we employed large databases and bioinformatics methods to identify genes strongly linked to PNI in colon cancer and investigated their involvement in tumor nerve invasion, progression mechanisms, and chemotherapy resistance. Immunohistochemical techniques were utilized to validate the expression of target genes in 384 colon cancer tissues, and their expression was correlated with clinicopathological characteristics and patient survival data in our hospital. Furthermore, we conducted a comprehensive literature review to explore the potential functions of the target genes and their associated genes. Results: Our screening revealed a significant correlation between neural proliferation differentiation and control-1 (NPDC1) expression and patient prognosis, suggesting a potential association with neural infiltration in colon cancer. Additionally, NPDC1 may promote tumorigenesis, progression, and chemoresistance through various related pathways. Conclusion: Our study provides novel insights into the utility of NPDC1 as a predictive marker for PNI status, disease-free survival, and overall survival in patients with colon cancer, highlighting the prevalence of NPDC1 overexpression in patients with PNI in colon cancer.

Case report: Surgical treatment of a primary giant epithelioid hemangioendothelioma of the spine with total en-bloc spondylectomy.

Background: Epithelioid hemangioendothelioma (EHE) is an extremely uncommon malignant neoplasm that originates from vascular endothelial or pre-endothelial cells. In this report, we present the case of patient who was diagnosed with a primary giant EHE of the spine and underwent treatment with total en-bloc spondylectomy (TES). Case presentation: A 43-year-old male patient with a history of he presented to our hospital with chronic and progressive back pain. Physical examination revealed weakened sensation of acupuncture and touch on the left costal arch, while relatively normal neurological functions were preserved. Radiological examinations identified a giant destructive soft tissue lesion occupying the T8 vertebral region, with moderate destruction of the pedicle and lamina, as well as the 7th left rib. A preoperative biopsy of the 8th vertebra resulted in a diagnosis of epithelioid hemangioendothelioma(EHE). Postoperative immunohistochemical and pathological reports confirmed the presence of EHE in the left ribs and T8 ribs. The patient underwent resection of the 7th left rib and posterior pedicle screw fixation with 8 pairs of screws and a titanium mesh cage. Subsequently, thoracic en bloc spondylectomy was performed on the T8 vertebra. The patient did not receive radiation or chemotherapy following surgery. Over a period of 3 years, the patient remained free of disease and relapse. Conclusion: The use of transarterial embolization with spherical embolic agents (TES) has been demonstrated to be a safe, effective, and reliable treatment option for hepatic epithelioid hemangioendothelioma (EHE). Nevertheless, it is crucial to conduct long-term follow-up of this patient in order to assess their clinical outcome.

AKT1 participates in ferroptosis vulnerability by driving autophagic degradation of FTH1 in cisplatin-resistant ovarian cancer.

Resistance to cisplatin (DDP)-based chemotherapy is an important reason for the failure of ovarian cancer treatment. However, tumor cells resistant to chemotherapy may expose vulnerability to other cell death pathways. Here, we found that DDP-resistant ovarian cancer cells are more susceptible to erastin-induced ferroptosis. It should be noted that this vulnerability does not depend on the weakening of classical ferroptosis defense proteins, but is caused by the reduction of ferritin heavy chain (FTH1). DDP-resistant ovarian cancer cells maintain a high level of autophagy to escape the pressure of chemotherapy, which ultimately leads to increased autophagic degradation of FTH1. We further revealed that the loss of AKT1 was the reason for the increased autophagy level of DDP-resistant ovarian cancer cells. Our study provides new insights into reversing DDP resistance in ovarian cancer by targeting ferroptosis pathway, and AKT1 may be a molecular marker of susceptibility to ferroptosis.

Silva cumulative score and its relationship with prognosis in Endocervical adenocarcinoma.

BACKGROUND: The Silva system has been demonstrated to have a good predictive value of lymph node metastasis (LNM) in endocervical adenocarcinoma (EAC). Tumours were classified based on the highest identified pattern of invasion in this system, this may not exactly reflect the true situation when it presents with a "mixed pattern" in some cases. Recent study has shown that patients with lymphovascular invasion (LVI) have worse prognosis in EAC. Here we design a Silva cumulative score (SCS) system which also combined the LVI status to explore its prognostic role in EAC patients. METHODS: A total of 120 patients with EAC were included in this study. Clinicopathological characteristics were retrospectively retrieved from the medical records and follow-up data were obtained. The clinicopathological information included age at diagnosis, depth of invasion (DOI), LNM, LVI, Silva classification, and SCS. SCS is a classification system based on the sum score of different Silva pattern which is founded on morphological phenomena. The relationships between the pathological characteristics and prognoses were analyzed. RESULTS: According to the Silva system, 11 (9.2%), 22 (18.3%) and 87 (72.5%) patients had patterns A, B, and C, respectively. Patients with pattern C had the highest incidence of LVI and LNM (p < 0.05). Although the Kaplan-Meier curves demonstrated that survival decreased with increasing Silva classification for A-C cancers, there was no statistically significant difference [disease-free survival (DFS): p = 0.181; overall survival (OS): p = 0.205]. There were 45 cases presented as mixed-type of Silva patterns. According to the SCS, 23 cases (19.2%) were rated as grade I, 31 cases (25.8%) as grade II and 66 (55.0%) cases as grade III. Patients with SCS grade III had the highest incidence of LVI and LNM (p < 0.05). Kaplan-Meier analysis revealed that patients with higher SCS had significantly shorter DFS and OS than those with lower SCS (p < 0.05). High SCS was an independent predictor of poorer OS and DFS (p < 0.05) in patients with EAC. CONCLUSIONS: The application of the Silva system could effectively predict the LNM of patients and may be helpful in selecting an appropriate surgical procedure. The SCS system we designed showed a good predictive value for DFS and OS in EAC.

Co-delivery of sorafenib and metformin from amphiphilic polypeptide-based micelles for colon cancer treatment.

Colorectal cancer (CRC) is a common clinical disease with a poor prognosis and a high recurrence rate. Chemotherapy is important to inhibit the post-surgical recurrence of CRC patients. But many limitations restrict the further application of chemotherapy. In this study, sorafenib (Sor) and metformin (Met) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) [mPEG-b-P(Glu-co-Phe)] micelles were developed. The characterizations, drug release, in vivo biodistribution, and pharmacokinetics of the micelles were analyzed. The treatment efficacy of the dual-drug loaded micelles was evaluated in a subcutaneous colon cancer mice model. Sor is a common molecular target agent that can inhibit the mitogen-activated protein kinase (MAPK) pathway to treat solid tumors. Met can also regulate the MAPK pathway and inhibit the expression of the phosphorylated extracellular signal-regulated kinase (p-ERK). Moreover, both Sor and Met play important roles in cell cycle arrest. The integration of these two drugs aims to achieve synergistic effects against colon cancer. The micelles can be targeted to cancer cells and possess longer blood circulation time. The two agents can be released rapidly in the tumor sites. The in vivo study showed that the micelles can prevent tumor progression by inhibiting the expressions of p-ERK and cyclin D1. This study indicated that the Sor/Met-loaded micelles are suitable for CRC treatment.

mPEG-b-P(Glu-co-Phe) nanoparticles increase gastric retention time and gastric ulcer treatment efficacy of 20(S)-ginsenoside Rg3.

BACKGROUND: Gastric ulcer (GU) belongs to gastric mucosal irritation and damage. 20(S)-ginsenoside Rg3 (Rg3) has shown anti-oxidant, antiinflammation, and tissue repair effects which are essential for GU treatment. However, the solubility of Rg3 is poor and low gastrointestinal absorption may limit its anti-ulcer effects. As a result, we aim to increase the gastric retention time and gastric absorption of Rg3 to achieve better GU treatment efficacy. METHODS: The mPEG-b-P(Glu-co-Phe) nanoparticles loaded with Rg3 (Rg3-NPs) were developed. The characteristics of Rg3-NPs, including the morphology, diameter, and stability were analyzed. The Rg3 release profiles, gastric retention of Rg3, in vitro cytotoxicity, and pharmacokinetics of Rg3 were assessed. An alcohol-induced rats GU model was performed, and the rats were randomly separated into five treatment groups. Biochemical analysis, gross evaluation, histopathology, and immunohistochemical analysis were applied to further analyze the anti-ulcer effects of Rg3-NPs. RESULTS: Rg3-NPs were successfully prepared and the Rg3 release was pH sensitive. The gastric retention time of Rg3 is longer in Rg3-NPs group than that in Rg3 group. By slightly increasing nitric oxide (NO), obviously increasing epidermal growth factor (EGF), EGF receptor (EGFR), and superoxide dismutase (SOD), and decreasing endothelin-1 (ET-1) and nitric oxide synthase (NOS2), Rg3-NPs possess better GU treatment efficacy than Rg3. CONCLUSIONS: Rg3-NPs can increase gastric retention time and gastric absorption of Rg3 and promote its GU treatment efficacy.

TTK predicts triple positive breast cancer prognosis and regulates tumor proliferation and invasion.

This study was conducted to investigate the expression of the spindle assembly checkpoint kinase tyrosine/threonine kinase (TTK) in triple positive breast cancer (TPBC) and its effect on TPBC cells. We analyzed the status of TTK in 69 TPBC samples using immunohistochemistry. The correlation between TTK and clinicopathological parameters was analyzed using a chi-squared test. The prognostic value of TTK was evaluated using Kaplan-Meier survival curves. We analyzed the role of TTK in the invasion and proliferation of TPBC cells in vitro and in vivo. The mean age of the 69 patients with TPBC enrolled in this study was 53 years (range: 29-86 years). TTK expression was positively correlated with tumor size (p=0.034), p53 status (p=0.023), TNM stage ([p=0.023), and Ki-67 index (p<0.001). The Kaplan-Meier curves revealed that TTK expression was correlated with poor disease-free survival (p=0.001) and overall survival (p=0.050). Multivariate proportional hazard regression analyses showed that TTK and TNM staging were significant independent predictors of disease-free survival (p=0.007 and p=0.034, respectively). Additionally, TTK knockdown inhibited the invasion and proliferation of the BT474 TPBC cell line. The findings of this study indicate that TTK overexpression is associated with cancer progression and prognosis in patients with TPBC, whereas TTK knockdown inhibits the invasion and proliferation of TPBC cells. Thus, TTK might serve as a prognostic marker for TPBC.

Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study.

BACKGROUND: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent. METHODS: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically. RESULTS: The study participants had a mean age of 59 years (range, 35-81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P <  0.001), necrotic/tumor debris (31 of 42; 73.8%; P <  0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P <  0.001), desmoplasia (35 of 41; 85.4%; P <  0.001), and grade 3 nuclei (12 of 14; 85.7%; P <  0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS. CONCLUSIONS: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.

PD-L1 expression and immune stromal features in HPV-independent cervical adenocarcinoma.

AIMS: Human papilloma virus (HPV)-independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD-1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD-ligand 1 (PD-L1). However, no data regarding PD-L1 expression in HPV-independent CA are available. Thus, we evaluated the association between PD-L1 expression and the clinicopathological characteristics and survival of patients with HPV-independent CA. METHODS: We evaluated PD-L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV-independent CA. PD-L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%. RESULTS: PD-L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD-L1 expression, based on either the CPS or the TPS, was associated with a high tumour-infiltrating lymphocyte percentage (CPS = P < 0.001; TPS = P < 0.001). Patients with a PD-L1 CPS ≥1 showed worse progression-free survival and overall survival than PD-L1-negative patients (P = 0.004 and P = 0.023, respectively). Forty-two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. CONCLUSIONS: Our data demonstrated that PD-L1 was expressed in HPV-independent CA, especially in clear cell carcinoma, and that PD-L1 expression is a negative prognostic marker. Our data support the role of PD-L1 in HPV-independent CA and its potential as an immunotherapeutic target.

Giant schwannoma of thoracic vertebra: A case report.

BACKGROUND: It is relatively rare for schwannomas to invade bone, but it is very rare for a large mass to form concurrently in the paravertebral region. Surgical resection is the only effective treatment. Because of the extensive tumor involvement and the many important surrounding structures, the tumor needs to be fully exposed. Most of the tumors are completely removed by posterior combined open-heart surgery to relieve spinal cord compression, restore the stability of the spine and maximize the recovery of nerve and spinal cord function. The main objective of this article is to present a schwannoma that had invaded the T5 and T6 vertebral bodies and formed a large paravertebral mass with simultaneous invasion of the spinal canal and compression of the spinal cord. CASE SUMMARY: A 40-year-old female suffered from intermittent chest and back pain for 8 years. Computed tomography and magnetic resonance imaging scans showed a paravertebral tumor of approximately 86 mm × 109 mm × 116 mm, where the adjacent T5 and T6 vertebral bodies were invaded by the tumor, the right intervertebral foramen was enlarged, and the tumor had invaded the spinal canal to compress the thoracic medulla. The preoperative puncture biopsy diagnosed a benign schwannoma. Complete resection of the tumor was achieved by a two-step operation. In the first step, the thoracic surgeon adopted a lateral approach to separate the thoracic tumor from the lung. In the second step, a spine surgeon performed a posterior midline approach to dissect the tumor from the vertebral junction through removal of the tumor from the posterior side and further resection of the entire T5 and T6 vertebral bodies. The large bone defect was reconstructed with titanium mesh, and the posterior root arch was nail-fixed. Due to the large amount of intraoperative bleeding, we performed tumor angioembolization before surgery to reduce and avoid large intraoperative bleeding. The postoperative diagnosis of benign schwannoma was confirmed by histochemical examination. There was no sign of tumor recurrence or spinal instability during the 2-year follow-up. CONCLUSION: Giant schwannoma is uncommon. In this case, a complete surgical resection of a giant thoracic nerve sheath tumor that invaded part of the vertebral body and compressed the spinal cord was safe and effective.

Analysis of Endoscopy Findings to Identify Early Gastric Cancers with Tumor Budding: A Retrospective Study.

BACKGROUND: No reliable method has been reported for determining tumor budding with frozen sections during surgical procedures. This study investigated endoscopic features predictive of tumor budding in early gastric cancers (EGC). METHODS: This retrospective study evaluated data from 137 patients diagnosed with EGC who underwent endoscopy, followed by endoscopic submucosal dissection (ESD); 71 patients underwent a second gastrectomy. Based on pathological analyses, lesions were categorized as being positive (n = 80) or negative for tumor budding (n = 57). Endoscopic features were analyzed using multivariable logistic regression. Patient survival rates were analyzed with Kaplan-Meier method and log-rank test. RESULTS: Mean age of our study population was 66 years (range, 31-86 years). The tumor budding-positive cohort (73.3 ± 5.9 years) was significantly older than the tumor budding-negative cohort (56.7 ± 7.6 years) (p < 0.001). Endoscopic features significantly different between tumor budding-positive and budding-negative groups included tumor size (p = 0.003), remarkable redness (p = 0.015), and margin elevation (p < 0.001). Tumor size (odds ratio (OR): 1.561; 95% confidence interval (CI): 0.984, 2.285; p = 0.047) and margin elevation (OR: 2.141; 95% CI: 1.147, 5.117; p = 0.003) were independent predictors of tumor budding. Margin elevation was found in 19.3% of tumor budding-negative and 53.8% of budding-positive cases. In the tumor budding-positive group, ESD and second gastrectomy were associated with disease-free survival. CONCLUSIONS: Margin elevation and large tumor size (> 29 mm) of EGCs on endoscopy are promising imaging biomarkers for predicting tumor budding in EGCs. ESD and a second gastrectomy can be better for tumor budding-positive patients with EGCs.

YAP increases response to Trastuzumab in HER2-positive Breast Cancer by enhancing P73-induced apoptosis.

The role of the Yes-associated protein (YAP) in oncogenesis and progression of breast cancer remains controversial. Meanwhile, development of therapeutic resistance to trastuzumab, a common breast cancer treatment administered after chemotherapy, is a significant challenge in the treatment of HER2-positive breast cancer. We, therefore, analyzed the role of YAP in trastuzumab resistance in HER2-positive-breast carcinoma cells in vitro and evaluated the status of YAP and related proteins in patient-derived breast carcinoma tissues by immunohistochemistry. YAP expression was observed in both BT474-TS (trastuzumab-sensitive) and BT474-TR (trastuzumab-resistant) cells. Treatment with trastuzumab increased expression of nuclear-YAP (N-YAP) in BT474-TS cells, whereas BT474-TR cells showed a decrease in N-YAP expression following trastuzumab treatment. YAP silencing significantly reduced trastuzumab-induced inhibitory effects in BT474-TS cells. YAP-silenced cells also showed decreased apoptosis and significantly lower p73 levels following trastuzumab treatment. Combined protein kinase B (AKT) inhibitor-trastuzumab treatment significantly inhibited BT474-TR cell proliferation, resulting in increased N-YAP and p73 expression, as well as apoptosis. In both paclitaxel, doxorubicin and cyclophosphamide (TAC)-treated, and docetaxel, carboplatin, and trastuzumab (TCbH)-treated groups; the pathological complete response (pCR) ratios were inversely correlated with p-AKT status in biopsy specimens, while YAP and p73 status were positively correlated with the pCR ratio in the biopsy specimens of the TCbH group. Our results show that YAP is involved in trastuzumab resistance in HER2-positive breast carcinoma cells and that YAP and AKT may be developed as prognostic markers of neoadjuvant trastuzumab therapy in patients with HER2-positive breast cancer.

Efficacy of mesenchymal stem cells in the treatment of gastrointestinal malignancies.

Mesenchymal stem cells (MSCs), which are a kind of stem cell, possess an immune privileged nature, tumour homing features, and multi-lineage differentiation ability. MSCs have been studied in many fields, such as tissue engineering, nervous system diseases, and cancer treatment. In recent years, an increasing number of researchers have focused on the effects of MSCs on various kinds of tumours. However, the concrete anticancer efficacy of MSCs is still controversial. Gastrointestinal (GI) malignancies are the major causes of cancer-related death worldwide. The interactions of MSCs and GI cancer cells in specific conditions have attracted increasing attention. In this review, we introduce the characteristics of MSCs and analyse the effects of MSCs on GI malignancies, including gastric cancer, hepatoma, pancreatic cancer, and colorectal cancer. In addition, we also provide our perspectives on why MSCs may play different roles in GI malignancies and further research directions to increase the treatment efficacy of MSCs on GI malignancies.

Desmoplastic Reaction and Tumor Budding in Cervical Squamous Cell Carcinoma are Prognostic Factors for Distant Metastasis: A Retrospective Study.

PURPOSE: An accurate risk assessment system for disease metastasis or recurrence could improve the cancer management practice in cervical squamous cell carcinoma (CxSCC) patients, which has few definite prognostic predictors. Previous studies have indicated the important utility of stromal features in determining cancer biological behavior; however, it lacks histopathologic or morphologic criteria for its evaluation. Therefore, this present study aimed to comprehensively catalog histopathological features of mesenchymal stroma to determine the prognostic value of these features in CxSCC. PATIENTS AND METHODS: We histologically and immunohistochemically evaluated the stromal features in the primary tumors of 122 CxSCC patients. The follow-up duration was 41.25 months (range: 3-80.77 months). Multivariate proportional hazard regression models were used to identify the top classifier for distant metastasis-free survival (DMFS) prediction. RESULTS: Lymph-vascular invasion (LVI), lymph node metastasis (LNM), tumor-node-metastasis (TNM) stage and tumor budding were positively correlated with distant metastasis (P < 0.001, P < 0.001, P < 0.001 and P = 0.012, respectively). Distant metastasis was also associated with the immature desmoplastic reaction (DR) (P = 0.002), high level of cancer-associated fibroblasts (P = 0.003), vasohibin-1 (VASH1)-positive microvessels (P = 0.027), and the VASH1/CD31 ratio (P = 0.004). Multivariate COX proportional hazard regression models revealed that LVI, LNM, and DR were independent predictors of poor DMFS in CxSCC patients. CONCLUSION: Primary tumor histologic stromal features, especially DR, may be useful in predicting distant metastasis in patients with CxSCC.

Clinicopathologic Features and Genetic Alterations in Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma of the Lung: Long-Term Follow-Up Study of 121 Asian Patients.

BACKGROUND: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are both small tumors with good prognosis after surgical resection, and most of them present as ground glass opacities (GGOs) on computed tomography (CT) screening. However, the differences in clinicopathologic features and genetic alterations between AIS and MIA are poorly elaborated, and few studies have evaluated the prognosis of MIA with different invasive components. Meanwhile, the histological features of lung lesions presenting as unchanged pure GGOs are barely understood. METHODS: Clinicopathologic features and genetic alterations of AIS (n = 59) and MIA (n = 62) presenting as GGOs were analyzed. Long-term preoperative observation (ranging from 2 to 1967 days) and postoperative follow-up (ranging from 0 to 92 months) was conducted. RESULTS: The tumor size and consolidation/tumor ratio were significantly larger in the MIA cohort than those in the AIS cohort both on CT and microscopy images. Immunohistochemically, the expression of p53, Ki67, and cyclin D1 was higher in MIA than in AIS. The EGFR mutation rate was significantly higher in MIA, while other genetic alterations showed no differences. Six MIA cases showed recurrence or metachronous adenocarcinoma and all the cases with a predominant micropapillary invasive pattern demonstrated this feature. CONCLUSIONS: The current CT measurements may be helpful in distinguishing AIS from MIA, but show limited utility in predicting the histology of unchanged pure GGOs. The invasive pattern may have an influence on the postoperative process of MIA; therefore, further studies are needed to evaluate the current diagnostic criteria and treatment strategy for MIA.

Immune stromal features in cervical squamous cell carcinoma are prognostic factors for distant metastasis: A retrospective study.

AIM: Malignant tumors are complex structures that must interact with the surrounding environment for growth and invasiveness. This study aimed to comprehensively catalogue the features of immune cell stromal infiltrates within tumor tissue and peri-tumoral tissue and to determine whether these features have prognostic value in cervical squamous cell carcinoma (CxSCC). METHODS: Immune stromal features in primary tumors in 122 patients enriched for CxSCC were histologically and immunohistochemically characterized. RESULTS: Distant metastasis was positively correlated with tumor-node-metastasis (TNM) stage (P < 0.001), lymph-vascular invasion (LVI) (P < 0.001), lymph node metastasis (LNM) (P < 0.001), and tumor budding (P = 0.012). Distant metastasis was also associated with the eosinophil infiltration (P = 0.006); Stromal, intratumoral, invasive-margin, squamous intraepithelial lesion (SIL), and perivascular tumor-infiltrating lymphocytes (TILs); CD68+, CD163+, and CD204+ macrophage infiltration. Multivariate proportional hazard regression analyses revealed that LVI; TNM stage; lymph node metastasis; tumor budding; eosinophil infiltration; CD163+ macrophage infiltration; and stromal and intratumoral TILs were independent predictors of poor DMFS in patients with CxSCC. CONCLUSION: Primary tumor immune stromal features can be useful in predicting distant metastasis in CxSCC.