Genetic and phenotypic determinants of morphologies in 3D cultures and xenografts of lung tumor cell lines.

We previously proposed the classification of lung adenocarcinoma into two groups: the bronchial epithelial phenotype (BE phenotype) with high-level expressions of bronchial epithelial markers and actionable genetic abnormalities of tyrosine kinase receptors and the non-BE phenotype with low-level expressions of bronchial Bronchial epithelial (BE) epithelial markers and no actionable genetic abnormalities of tyrosine kinase receptors. Here, we performed a comprehensive analysis of tumor morphologies in 3D cultures and xenografts across a panel of lung cancer cell lines. First, we demonstrated that 40 lung cancer cell lines (23 BE and 17 non-BE) can be classified into three groups based on morphologies in 3D cultures on Matrigel: round (n = 31), stellate (n = 5), and grape-like (n = 4). The latter two morphologies were significantly frequent in the non-BE phenotype (1/23 BE, 8/17 non-BE, p = 0.0014), and the stellate morphology was only found in the non-BE phenotype. SMARCA4 mutations were significantly frequent in stellate-shaped cells (4/4 stellate, 4/34 non-stellate, p = 0.0001). Next, from the 40 cell lines, we successfully established 28 xenograft tumors (18 BE and 10 non-BE) in NOD/SCID mice and classified histological patterns of the xenograft tumors into three groups: solid (n = 20), small nests in desmoplasia (n = 4), and acinar/papillary (n = 4). The latter two patterns were characteristically found in the BE phenotype. The non-BE phenotype exhibited a solid pattern with significantly less content of alpha-SMA-positive fibroblasts (p = 0.0004) and collagen (p = 0.0006) than the BE phenotype. Thus, the morphology of the tumors in 3D cultures and xenografts, including stroma genesis, reflects the intrinsic properties of the cancer cell lines. Furthermore, this study serves as an excellent resource for lung adenocarcinoma cell lines, with clinically relevant information on molecular and morphological characteristics and drug sensitivity.

ZEB1 expression is frequently detected in undifferentiated and de-differentiated carcinomas, but is not specific among endometrial carcinomas.

AIMS: The pathological diagnosis of undifferentiated and de-differentiated endometrial carcinomas (UC/DCs) is prognostically important. However, undifferentiated components may be confused with other subtypes, particularly grade 3 endometrioid carcinomas (G3ECs). Zinc finger E-box binding homeobox 1 (ZEB1) has recently been identified as a promising marker because it is frequently expressed in the undifferentiated components of UC/DCs, but not in other carcinomas. Therefore, we herein evaluated the diagnostic utility of ZEB1 with an emphasis on distinguishing between UC/DCs and G3ECs using an expanded cohort of endometrial carcinomas and carcinosarcomas. METHODS AND RESULTS: Immunostaining for ZEB1 was performed on whole-tissue sections of 19 UC/DCs, 194 non-UC/DC endometrial carcinomas and 29 carcinosarcomas. Staining was defined as negative (< 5%), focal (5-50%) and diffuse expression (> 50%). ZEB1 was expressed in 84% of the undifferentiated components of UC/DCs (diffuse in 14, focal in two). Focal expression was observed in eight non-UC/DC endometrial carcinomas and diffuse expression in seven, with the latter comprising G3ECs (four of 76), serous carcinoma (one of 37), clear cell carcinoma (one of 21) and neuroendocrine carcinoma (one of three). Epithelial differentiation was morphologically and immunohistochemically less evident in G3ECs and neuroendocrine carcinoma with diffuse ZEB1 expression. All carcinosarcomas showed diffuse ZEB1 expression in their sarcomatous components. CONCLUSION: Immunostaining for ZEB1 was sufficiently sensitive to detect undifferentiated components. Diffuse ZEB1 expression showed high specificity for distinguishing between undifferentiated components and G3ECs; however, ZEB1 expression was not entirely specific to UC/DCs. The integration of ZEB1 into the diagnosis of UC/DCs requires careful examination to exclude other tumours, such as less differentiated G3ECs, neuroendocrine carcinomas and carcinosarcomas.

Ovarian clear cell carcinoma with an immature teratoma component showing ARID1A deficiency and an identical PIK3CA mutation.

We herein report a case of ovarian clear cell carcinoma with an immature teratoma component that exhibited aggressive behavior. A 47-year-old woman presented with abdominal distention, and computed tomography detected a cystic mass on the right ovary. The resected mass had mural nodules, most of which showed a pale-yellow appearance; some nodules had a heterogeneous cut surface with bright yellow and white areas. Histologically, the former nodules were composed of clear cell carcinoma, while the latter contained teratomatous tissues, such as immature skeletal muscle, adipose tissue, and enteric glands. The tumor was staged as pT1c. Despite adjuvant chemotherapy and additional lymph node dissection, she had local recurrence and multiple liver metastasis 6 months after the first surgery. The disease rapidly progressed, and she died 9 months after the first surgery. Clear cell carcinoma and immature teratoma both showed ARID1A deficiency and an identical PIK3CA mutation, which suggested their clonal relationship.

Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas.

Molecular targeted therapies against EGFR and ALK have improved the quality of life of lung adenocarcinoma patients. However, targetable driver mutations are mainly found in thyroid transcription factor-1 (TTF-1)/NK2 homeobox 1 (NKX2-1)-positive terminal respiratory unit (TRU) types and rarely in non-TRU types. To elucidate the molecular characteristics of the major subtypes of non-TRU-type adenocarcinomas, we analyzed 19 lung adenocarcinoma cell lines (11 TRU types and 8 non-TRU types). A characteristic of non-TRU-type cell lines was the strong expression of TFF-1 (trefoil factor-1), a gastric mucosal protective factor. An immunohistochemical analysis of 238 primary lung adenocarcinomas resected at Jichi Medical University Hospital revealed that TFF-1 was positive in 31 cases (13%). Expression of TFF-1 was frequently detected in invasive mucinous (14/15, 93%), enteric (2/2, 100%), and colloid (1/1, 100%) adenocarcinomas, less frequent in acinar (5/24, 21%), papillary (7/120, 6%), and solid (2/43, 5%) adenocarcinomas, and negative in micropapillary (0/1, 0%), lepidic (0/23, 0%), and microinvasive adenocarcinomas or adenocarcinoma in situ (0/9, 0%). Expression of TFF-1 correlated with the expression of HNF4-α and MUC5AC (P < .0001, P < .0001, respectively) and inversely correlated with that of TTF-1/NKX2-1 (P < .0001). These results indicate that TFF-1 is characteristically expressed in non-TRU-type adenocarcinomas with gastrointestinal features. The TFF-1-positive cases harbored KRAS mutations at a high frequency, but no EGFR or ALK mutations. Expression of TFF-1 correlated with tumor spread through air spaces, and a poor prognosis in advanced stages. Moreover, the knockdown of TFF-1 inhibited cell proliferation and soft-agar colony formation and induced apoptosis in a TFF-1-high and KRAS-mutated lung adenocarcinoma cell line. These results indicate that TFF-1 is not only a biomarker, but also a potential molecular target for non-TRU-type lung adenocarcinomas.

Desmoplastic small round cell tumor showing solid proliferation with limited desmoplasia and confusing immunohistochemical findings: an autopsy report.

We herein report a variant case of desmoplastic small round cell tumor (DSRCT) showing limited desmoplasia and confusing immunohistochemical findings. A 26-year-old male was referred for multiple abdominal masses. Laparoscopic biopsy showed only the solid proliferation of small round cells, and he was initially diagnosed with small cell carcinoma. At autopsy, the tumor spread diffusely throughout the abdominal and pelvic cavities. Although the tumor was composed of a predominantly solid pattern of small round cells, multiple samples revealed a fibrous stroma in limited areas only. While immunohistochemistry showed the diffuse expression of desmin, CD99, and bcl-2, epithelial differentiation was unclear with few cytokeratin-positive cells and no staining for the epithelial membrane antigen. Although fluorescence in situ hybridization analysis indicated the EWSR1 gene rearrangement, we were unable to exclude Ewing sarcoma considering the morphological and immunohistochemical findings. The diagnosis of DSRCT was confirmed with a reverse transcription-polymerase chain reaction for EWSR1-WT1 fusion transcripts. DSRCT must be included in a differential diagnosis of small round cell tumors even if desmoplasia is not immediately detected, and thorough sampling and a molecular analysis are mandatory.

Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma.

Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell-cell and cell-matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O-glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness.

SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomas.

AIMS: To investigate how SNAIL and SLUG were involved in the nature of high-grade endometrial carcinomas (grade 3 endometrioid carcinoma, serous carcinoma and clear cell carcinoma), we analysed the correlation of their expression status with clinicopathological characteristics and evaluated their prognostic significance. METHODS AND RESULTS: We performed immunohistochemical staining in 52 high-grade endometrial carcinomas. Expression status of SNAIL and SLUG was classified into a high expression (positive in more than 50% of the tumour cells) and a low expression. Thirteen cases (25%) showed a high expression of SLUG, whereas all 52 cases showed a low expression of SNAIL. High expression of SLUG was correlated significantly with tumour recurrence (P = 0.0203) and aberrant p53 expression (P = 0.000559). Overall survival was worse in patients with high SLUG expression at all stages (P = 0.0327) and in those who underwent adjuvant therapy (P = 0.00963). Among the patients with complete tumour resection, high SLUG expression was associated with worse recurrence-free survival (RFS) in the patients at all stages (P = 0.00264), at stages III/IV (P = 0.0146), and who underwent adjuvant therapy (P = 0.000743). SLUG expression was identified as an independent factor of RFS by multivariate analysis (hazard ratio 5.938, 95% confidence interval 1.251-28.18, P = 0.025). CONCLUSIONS: SLUG expression could be correlated with TP53 mutational status and could be involved in therapeutic resistance resulting in tumour recurrence. A high expression level of SLUG can be an indicator of recurrence and a therapeutic target for long-term remission in high-grade endometrial carcinomas.

The significance of Hippo pathway protein expression in oral squamous cell carcinoma.

Introduction: The Hippo pathway consists of mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC). Methods: The analyses included oral epithelial dysplasia (OED, n = 7), carcinoma in situ (CIS, n = 14), and oral squamous cell carcinoma (OSCC, n = 109). Results: Cytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5/7 cases), CIS (9/14 cases), and poorly differentiated OSCC (8/8 cases) but was low/lost in a proportion of differentiated OSCC (60/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35/71 cases), compared to moderately and poorly differentiated OSCC (11/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (p < 0.0001). Conclusion: Among the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.

Successfully Resected Isolated Lateral Lymph Node Recurrence in a Patient with T1 Lower Rectal Cancer: Case Report and Literature Review.

Lateral lymph node (LLN) metastasis in T1 rectal cancer has an incidence of less than 1%. However, its clinical features are largely uncharted. We report a case of LLN metastasis in T1 rectal cancer and review the relevant literature. A 56-year-old female underwent rectal resection for lower rectal cancer 2 years previously (pT1bN0M0). During follow-up, an elevated tumor marker CA19-9 was documented. Enhanced CT and MRI showed a round shape nodule 2 cm in size on the left side of pelvic wall. PET-CT showed high accumulation of FDG in the same lesion, leading to a diagnosis of isolated LLN recurrence. Because no other site of recurrence was detected, surgical resection of the LLN was performed. Microscopic findings were consistent with metastatic lymph node originating from the recent rectal cancer. Adjuvant chemotherapy for six months was given, and patient remains free of recurrent disease seven months after LLN resection. Although LLN recurrence after surgery for T1 rectal cancer is rare, post-surgical follow-up should not be omitted. When LLN metastasis is suspected on CT, MRI and/or PET-CT will be recommended. Surgical resection of LLN metastasis in patients with T1 rectal cancer may lead to favorable outcomes, when recurrence in other areas is not observed.

Guanylate binding protein 5 is an immune-related biomarker of oral squamous cell carcinoma: A retrospective prognostic study with bioinformatic analysis.

BACKGROUND: Cancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis. METHODS: First, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed. RESULTS: Among the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival. CONCLUSIONS: The stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors.

Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.

INTRODUCTION: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND METHODS: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression. RESULT: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors. CONCLUSION: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.

H3K27me3 deficiency in dedifferentiated carcinoma and carcinosarcoma of the endometrium.

The present study immunohistochemically investigated trimethylation of lysine 27 of histone 3 (H3K27me3) expression in 769 endometrial carcinomas and 196 uterine mesenchymal tumors. One dedifferentiated endometrial carcinoma (DEC) and one carcinosarcoma showed H3K27me3 deficiency that was limited to undifferentiated and sarcomatous components, respectively. Switch/sucrose nonfermenting (SWI/SNF) complex subunits (SMARCA4, SMARCB1, and ARID1A/1B) and mismatch repair proteins were proficient in both tumors. The dimethylation of H3K27 (H3K27me2) was deficient in the undifferentiated component, whereas the sarcomatous component had scattered H3K27me2-positive cells. CXorf67, which inhibits PRC2 function, was diffusely expressed in the sarcomatous component. CXorf67 was negative in the undifferentiated component, which was submitted to a genetic analysis and showed no alterations in PRC2 core subunits or H3K27. The present results suggest H3K27 methylation dysregulation as a cause of SWI/SNF-proficient DEC and carcinosarcoma and imply differences in their level of and the mechanisms underlying H3K27 methylation dysregulation.

Transduodenal ampullectomy for early ampullary cancer: Clinical management, histopathological findings and long-term outcomes at a single center.

BACKGROUND: Transduodenal ampullectomy has been attempted in ampullary tumors, including early ampullary cancer. However, the indication and extent of transduodenal ampullectomy with curative intent remain controversial. Herein, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent transduodenal ampullectomy at a single center. METHODS: We retrospectively enrolled 10 early ampullary cancer patients who underwent transduodenal ampullectomy and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy at Saitama Cancer Center between October 2008 and May 2021. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. RESULTS: In terms of the perioperative outcomes between the transduodenal ampullectomy and subtotal stomach-preserving pancreatoduodenectomy groups, the transduodenal ampullectomy group exhibited a shorter operating time (244 minutes vs 390 minutes, P = .003), less intraoperative blood loss (67.5 grams vs 774 grams, P = .006) and shorter length of postoperative hospital stay (15 days vs 33 days). With respect to the postoperative nutrition status, the transduodenal ampullectomy group exhibited less postoperative weight loss (0.67% vs 8.95%, P = .021), a better Controlling Nutritional Status score (1.0 vs 2.1, P = .011) and a better Prognostic Nutritional Index score (42.9 vs 40.9, P = .018). The 5-year survival in the adenoma with high-grade dysplasia and T1 ampullary cancer which invaded the mucosal layer groups was 100%, whereas the median survival time in the T1 ampullary cancer which invaded the sphincter of Oddi group was 20.7 months (P = .0028). CONCLUSION: Transduodenal ampullectomy is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with high-grade dysplasia or T1 ampullary cancer which invaded the mucosal layer ampullary cancer.

An adult case of midgut volvulus in familial visceral myopathy.

We report an adult case of midgut volvulus in familial visceral myopathy (FVM) that had affected family members over three generations. The patient was a Japanese woman in her fifties, who had chronic intestinal pseudo-obstruction (CIPO) since the age of about 40 years and had been treated chronically with conservative therapies. Her abdominal symptoms suddenly worsened and surgery became necessary. Surgery revealed a midgut volvulus secondary to intestinal malrotation and the twisted intestine was resected. Histology revealed diffuse damage of myocytes confined to the muscularis propria throughout the resected intestine. The myocytes were irregulary arranged, contained cytoplasmic inclusions, and had mild and focal vacuolar changes. The mucsularis propria showed hypertrophy with delicate interstitial fibrosis. A diagnosis of FVM was made on the basis of this characteristic myopathy. Intestinal malrotation is known to be a complication of CIPO in children, but is rare in adults. Although midgut volvulus appears to be extremely rare, it can occur after a relatively stable chronic phase in adult CIPO patients, who should be monitored carefully to assess the risk of such complications.

Expression and localisation of methylthioadenosine phosphorylase (MTAP) in oral squamous cell carcinoma and their significance in epithelial-to-mesenchymal transition.

Methylthioadenosine phosphorylase (MTAP) is a rate-limiting enzyme in the methionine salvage pathway, which recycles one carbon unit that is lost during polyamine synthesis back into the methionine cycle. Although MTAP deficiency has been reported in various tumours, MTAP is overexpressed and might promote oncogenesis in other cancers, including prostate and colon cancer. Currently, little is known about the MTAP status of oral squamous cell carcinoma (OSCC). In this study, we immunohistochemically examined the expression of MTAP in surgically resected oral epithelial dysplasia (OED, n=7), carcinoma in situ (CIS) (n=16), and OSCC (n=118). In the normal epithelium, MTAP was only weakly expressed in the cytoplasm of the basal layer cells. In OED, CIS, and OSCC, MTAP was uniformly expressed in the cytoplasm of the dysplastic and cancer cells. In addition to cytoplasmic MTAP expression, 45 of 118 cases (38.1%) exhibited increased nuclear expression of MTAP in the cancer cells at the invasive front. Statistical analysis showed that the concomitant nuclear and cytoplasmic expression of MTAP was associated with a high budding score (p=0.0023); poor differentiation (p=0.0044); aggressive invasion patterns (p=0.0001); and features of epithelial-to-mesenchymal transition (EMT), such as loss of E-cadherin expression (p=0.0003) and upregulated expression of vimentin (p=0.0002), slug (p=0.0002), and laminin 5 (p<0.0001). High expression of protein arginine methyltransferase 1 or 5, the functions of which are reported to be inhibited in MTAP-deficient cancer, was associated with the concomitant nuclear and cytoplasmic expression of MTAP (p<0.0001). Concomitant nuclear and cytoplasmic expression of MTAP was marginally significantly associated with worse 5-year relapse-free survival (p=0.045). These findings suggest that MTAP not only plays a role in the oncogenesis of OSCC, but that it might also make it more aggressive by inducing EMT through its activity in the methionine salvage pathway.

Conversion surgery for initially unresectable advanced biliary tract cancer treated with gemcitabine plus cisplatin combination chemotherapy: a case report and literature review.

Recently, the number of reports describing patients with initially unresectable biliary tract cancer (BTC) who underwent resection in the form of conversion surgery is increasing. Gemcitabine plus cisplatin (GC) combination therapy has been reported to significantly prolong the median survival time from 8.1 to 11.7 months compared with conventional gemcitabine therapy in patients with unresectable BTC. We report the case of a patient with unresectable BTC who underwent conversion surgery with a partial response to GC combination therapy. A 78-year-old woman was diagnosed with unresectable BTC with invasion of the right hepatic artery by lymph node metastasis and liver metastases. The patient received GC combination therapy. After 6 cycles of chemotherapy, the patient achieved a partial response. The radiological findings revealed a marked shrinkage in the primary lesion and the disappearance of lymph node and liver metastases. Therefore, the patient underwent conversion surgery, including biliary tract resection and regional lymph node dissection. For postoperative follow-up, the patient was monitored without receiving adjuvant chemotherapy. The patient had not exhibited recurrence during the 12-month follow-up period. We report the case of a patient with unresectable BTC who underwent conversion surgery with a partial response to GC combination therapy.

Clinicopathological and Prognostic Significance of Stromal Patterns in Oral Squamous Cell Carcinoma.

Background: Stromal patterns (SP), especially desmoplastic reactions, have recently gained attention as indicators of malignant potential in cancer. In this study, we explored the clinicopathological and prognostic significance of the SP in oral squamous cell carcinoma (OSCC). Materials and Methods: We reviewed 232 cases of surgically resected OSCC that were not treated with neoadjuvant chemoradiotherapy. We categorized the SP of the OSCC into four groups: immune/inflammatory (84 cases), mature (14 cases), intermediate (78 cases), or immature (56 cases). Results: The SP category was significantly associated with various clinicopathological factors, such as the histological grade, lymphovascular invasion, neural invasion, and a diffuse invasion pattern. For each of the factors, the immune/inflammatory type was associated with favorable categories, while the immature type was associated with unfavorable categories (p ≤ 0.001). The SP category was also shown to be a prognostic predictor: the 5-year relapse-free survival (RFS) rate was 72.0% for the immune/inflammatory type, 66.7% for the intermediate/mature type, and 31.2% for the immature type (p < 0.0001), and the 5-year overall survival (OS) rate was 85.1% for the immune/inflammatory type, 76.4% for the intermediate/mature type, and 50.0% for the immature type (p < 0.0001). In multivariate analyses, the SP category was identified as an independent prognostic factor for RFS and OS. Conclusion: Our SP categorization method provides valuable prognostic information in OSCC.