SOX17 expression in tumor-penetrating vessels in relation to CD8+ T-cell infiltration in cancer stroma niches.

INTRODUCTION: Sex-determining region Y-related high-mobility group box 17 protein (SOX17), a proangiogenic transcription factor, is specifically expressed in tumor endothelial cells (TECs) of implanted Lewis lung carcinoma. However, the expression profile of SOX17 is largely unknown in human lung cancer. We aimed to elucidate SOX17 expression in cancer cells and the tumor microenvironment of lung adenocarcinoma. METHODS: In the present study, we examined SOX17 expression in whole-tissue specimens of 83 lung adenocarcinomas by immunohistochemistry. RESULTS: SOX17 immunoreactivity was minimal in lung adenocarcinoma cells, except in five non-mucinous adenocarcinomas in situ. SOX17 was also expressed in cultured A549 lung adenocarcinoma cells, which is widely used as a model of malignant alveolar type II epithelial cells. Notably, SOX17 immunoreactivity was found in endothelial cells of tumor-penetrating vessels in 19 of 83 lung adenocarcinoma tissue specimens, with statistical significance to stromal infiltration of CD8+ T cells (p < 0.01) but was not associated with the number of tertiary lymph nodes. Although not statistically significant, SOX17 immunoreactivity was related to favorable patient outcomes. CONCLUSION: Our findings indicate that SOX17 might play a pleiotropic role in lung adenocarcinoma in cancer cells and stromal niches. SOX17-mediated CD8+ T-cell-rich tumor microenvironment might attract interest in improving the effect of cancer immunotherapy.

Effect and mechanisms of cyclophosphamide-induced ovarian toxicity on the quality of primordial follicles with respect to age at treatment initiation.

Chemotherapy-induced ovarian toxicity in patients with cancer significantly affects future fertility depending on the age of initiation of treatment. However, the mechanisms underlying the age-related depletion of the ovarian reserve are not well understood. We investigated the effects of chemotherapy on pre- and postpubertal ovarian reserves in a mouse model. Juvenile (3-week-old) and adult (8-week-old) mice were injected with vehicle or cyclophosphamide (CPA;100 mg/kg). We assessed the short-term effects at 24 h and 72 h after injection and the long-term effects at 10 and 12 weeks of age by counting the follicles. The number of primordial follicles in the juvenile group was significantly reduced by CPA treatment compared with that in the adult group. To elucidate the mechanisms of this depletion, we performed immunostaining for γH2AX, cleaved PARP1, and FOXO3 at 24 h post-treatment. CPA-treated juvenile mice had a significantly higher proportion of γH2AX-positive primordial follicles, indicating double-strand DNA breaks. By contrast, 4-hydroperoxy CPA, an activated analog of CPA, induced γH2AX-positive primordial follicles in both groups in vitro, suggesting age-dependent differences in humoral ovarian microenvironment. Moreover, the level of cleaved PARP1 was specifically elevated in CPA-treated juvenile mice. However, primordial follicle activation was unaffected in the CPA-treated groups, as assessed by FOXO3 translocation. In conclusion, our findings suggest that ovaries in juveniles are more susceptible to DNA damage and subsequent apoptosis, leading to a higher rate of primordial follicle depletion. Therefore, it is crucial to recognize that cancer treatment, especially in children, can exert a substantial influence on future fertility.

Successful Surgical Resection of Pancreatic Arteriovenous Malformation Complicated by Acute Pancreatitis: A Case Report.

A 73-year-old man presented with left hypochondral pain. Dynamic computed tomography (CT) revealed abnormal vessels surrounding the pancreas, leading to a suspected diagnosis of pancreatic arteriovenous malformation (PAVM). At the time of the initial examination, dynamic CT revealed mild acute pancreatitis, and PAVM was diagnosed based on the findings of dynamic CT. Although repeated abdominal pain was observed after the improvement of pancreatitis, distal pancreatectomy was performed. At >1 year after surgery, no recurrence of PAVM was observed. Surgical resection should be considered in patients with symptomatic PAVM.

SOX17 expression in tumor endothelial cells in colorectal cancer and its association with favorable outcomes in patients.

The high mortality rate of colorectal cancer (CRC) highlights the need for new treatment strategies; however, the venous invasion mechanisms in tumor endothelial cells within CRC remain unexplored. Therefore, we investigated the clinicopathological features of SRY-box transcription factor 17 (SOX17) in CRC. Immunohistochemical staining was performed on 55 CRC tissue specimens using a SOX17-specific antibody, followed by Kaplan-Meier and Cox proportional hazards regression analyses. SOX17 immunoreactivity was detected in the endothelial cells of tumor-penetrating vessels in 35/55 CRC samples. Kaplan-Meier analysis indicated that patients with SOX17 immunoreactivity had favorable overall and progression-free survival (log-rank test, P = 0.03 and 0.02, respectively). Notably, tumor endothelial SOX17 immunoreactivity was associated with a favorable prognosis in patients with stage III or IV disease (OS, P = 0.0089; PFS, P = 0.0065). Cox proportional hazard regression analysis indicated that SOX17 immunoreactivity is an independent factor for predicting favorable overall and progression-free survival in CRC (P = 0.02 and 0.01, respectively). The present findings suggest that SOX17 expression in tumor endothelial cells is a potential indicator of favorable prognosis in patients with CRC.

Successful R0 resection after chemotherapy, including nivolumab, for gastric cancer with liver metastases: three case reports.

BACKGROUND: Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response. CASE PRESENTATION: In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells. CONCLUSIONS: We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.

Discrepancy in the Location of Prostate Cancer Indicated on Biparametric Magnetic Resonance Imaging and Pathologically Diagnosed Using Surgical Specimens.

Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.

Inducing Melanoma Cell Apoptosis by ERp57/PDIA3 Antibody in the Presence of CPI-613 and Hydroxychloroquine.

The combination of the cancer mitochondrial metabolic inhibitor CPI-613 and hydroxychloroquine has tumor-suppressive effects on clear cell sarcoma, which shares pathobiological properties with melanoma. Therefore, we intended to examine the effects of a combination of CPI-613 and hydroxychloroquine on the growth of melanoma cells in the present study. However, cell death was not induced in melanoma cells. Therefore, a monoclonal antibody, ICT, that induced apoptosis in melanoma cells in combination with CPI-613 and hydroxychloroquine was developed. Immunoprecipitation, mass spectrometry, and small interfering RNA (siRNA)-mediated gene silencing demonstrated that ICT targeted Endoplasmic Reticulum Resident Protein 57/ Protein Disulfide Isomerase Family A Member 3 (ERp57/PDIA3), which was first identified as being upregulated by metabolic depletion stress and is localized on the cell surface during immunogenic cell death. The combination of CPI-613 and hydroxychloroquine enhanced the localization of ERp57/PDIA3 to the surface of melanoma cells. siRNA-mediated downregulation of ERp57/PDIA3 did not significantly induce ICT-mediated apoptosis in melanoma cells in the presence of CPI-613 and hydroxychloroquine. Therefore, the ICT antibody acts as a tumor suppressor in melanoma cells by targeting the cell membrane ERp57/PDIA3, expression of which was enhanced by the combination of CPI-613 and hydroxychloroquine.

Expression of IZUMO2 in colorectal cancer in association with clinicopathological features.

IZUMO2 belongs to the testis-expressed IZUMO family of proteins, which are characterized by an N-terminal IZUMO domain. Based on integrated analysis of expression profiles and matched DNA methylation data from a public database, IZUMO2 represents a prognosis-related methylation-driven gene in colorectal cancer. However, it remains unclear whether IZUMO2 protein expression is suppressed or overexpressed in colorectal cancer cells. In this study, we aimed to elucidate the expression of the IZUMO2 protein in colorectal cancer, with a focus on the clinicopathological features. Sixty-four colorectal cancer tissue specimens were immunohistochemically stained using specific antibodies against IZUMO2. IZUMO2 immunoreactivity was detected at the invasion front in 30 of the 64 colorectal cancer samples. Kaplan-Meier analysis demonstrated that patients with IZUMO2 immunoreactivity had a relatively shorter overall and progression-free survival (log-rank test, P = 0.046 and 0.019, respectively). IZUMO2 immunoreactivity served as an independent factor predictive of poor progression-free survival in colorectal cancer (P = 0.025) as determined via the Cox proportional hazard regression model. Moreover, IZUMO2 immunoreactivity represented an independent factor for poor overall survival (P = 0.035) and progression-free survival (P = 0.013) in patients with colon cancer. The present findings suggest that IZUMO2 is expressed in many colorectal cancers, especially at the cancer invasion front, and may represent an indicator of poor prognosis in colorectal cancer.

Implication of IZUMO2 in the cell-in-cell phenomenon: A potential therapeutic target for triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by the loss of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The aggressive clinicopathological features and resistance to currently available therapeutics of the disease warrant an urgent need for the development of novel alternate therapeutic options. We have previously reported adiponectin-expressing regulatory T cells (A-Tregs), which can induce apoptosis in TNBC through the cell-in-cell phenomenon. In this study, we aimed to elucidate the molecule that allows TNBC cells to engulf A-Tregs. METHODS: A monoclonal antibody, which repressed the engulfment of A-Tregs by TNBC cells, was developed. Immunoprecipitation followed by mass spectrometry and small interfering RNAs-mediated gene silencing was performed to characterize the antigen. RESULTS: We successfully generated a monoclonal antibody, designated G1D7, which abrogated the engulfment of A-Tregs by TNBC and subsequent A-Treg-mediated apoptosis. G1D7 detected the immunoglobulin-like type I membrane protein IZUMO2, a molecule related to IZUMO1 that is essential for cell-cell membrane binding and fusion of sperm to oocyte. CONCLUSION: The findings highlight the importance of IZUMO2 on TNBC cells in facilitating the cell-in-cell phenomenon by A-Tregs.

Balamuthia mandrillaris amoebic encephalitis mimicking tuberculous meningitis.

A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.

Adiponectin-expressing Treg-containing T cell fraction inhibits tumor growth in orthotopically implanted triple-negative breast cancer.

BACKGROUND: In our previous study, we identified a population of adiponectin expressing regulatory T cells (Tregs) residing within thymic nurse cell complexes, which were capable of inhibiting the development of breast cancer in vitro. Triple-negative breast cancer (TNBC) with no proper treatment at present is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. In this study, we aimed to investigate the potential of a cultured T cell fraction comprising adiponectin-expressing Tregs, referred to as A-TregTF (adiponectin-expressing Treg-containing T cell fraction), in inhibiting the progression of TNBC in vivo. METHODS: The efficacy of a spontaneously expanding T cell fraction comprising adiponectin-expressing Treg in inhibiting tumor growth was analyzed in a murine orthotopic 4 T1-Luc TNBC model. RESULTS: The treatment with T cell fraction containing adiponectin-expressing Tregs significantly inhibited the growth and metastasis of orthotopically transplanted 4 T1-Luc tumor cells. Histopathological examination further revealed that the adiponectin-expressing Tregs infiltrated the tumor tissue via a cell-in-cell mechanism and were found to be specifically localized around the necrotic areas. CONCLUSIONS: Based on our findings, the T cell fraction comprising adiponectin-expressing Tregs, represents a potential candidate for adoptive cell therapy against TNBC.

Late recurrent gastric carcinoma 12 years after surgery with attenuation of CD44 variant 9 expression.

BACKGROUND: Late recurrence of gastric cancer at 10 years post-gastrectomy is extremely rare, and the underlying mechanism remains unclear. We report a para-aortic lymph node metastasis case that recurred 12 years postoperatively. CASE PRESENTATION: A 44-year-old woman pathologically diagnosed with moderately to poorly differentiated adenocarcinoma with pT2(SS)pN2cM0pStageIIIA according to the Japanese Classification of Gastric Carcinoma (the 13th Edition) underwent laparoscopic distal gastrectomy with D1 + lymph node dissection. She received adjuvant chemotherapy with tegafur-uracil (400 mg/day) for 2 years. At postoperative year (POY) 5, a swollen lymph node was detected in the No.16b1lat lymph node station. However, positron emission tomography (PET) revealed normal uptake, and the levels of tumor markers were within normal limits; hence, the possibility of metastasis was considered low, and the patient was placed under observation. At POY 12, computed tomography revealed an enlargement of the No.16b1lat lymph node station, and PET showed abnormal uptake. Endoscopic ultrasound-guided fine-needle aspiration revealed a moderately differentiated adenocarcinoma. Hence, a diagnosis of recurrence of gastric cancer was made. The patient underwent para-aortic nodal dissection (PAND) of No.16b1lat & int stations. Immunochemical staining results also suggested the recurrence of gastric cancer. However, the expression of CD44 variant 9 (CD44v9), a cancer stem cell marker for gastric adenocarcinoma, was attenuated in the recurrent lesions compared with that in the primary lesions. Postoperatively, she received chemotherapy with tegafur-gimeracil-oteracil (80 mg/day) for 1 year. Bone metastasis was observed at POY 4 after PAND, and the IHC analysis showed a HER2 score of 3 + in a needle biopsy specimen of bone metastasis. The expression of CD44v9 was slightly positive. The patient is being treated with chemotherapy with FOLFOX + trastuzumab. CONCLUSIONS: A defense mechanism against reactive oxygen species has been reported as a mechanism causing recurrence of CD44v9-positive gastric cancer. Consequently, CD44v9-positive gastric cancer grows in metastatic organs, repeatedly self-renews, and proliferates to form recurrent lesions. In the present case, the degree of CD44v9 staining in recurrent lesions was suggested to be related to the recurrence time.

Potential activity of adiponectin-expressing regulatory T cells against triple-negative breast cancer cells through the cell-in-cell phenomenon.

BACKGROUND: A population of regulatory T cells (Treg), which reside within thymic nurse cell complexes, express adiponectin and abrogate breast cancer development in transgenic mice. In this study, we examined whether adiponectin-expressing Treg could impair triple-negative breast cancer, which is defined by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2. METHODS: CD4- and CD25-positive cells were sorted from cultured T lymphocytes of a previously characterized experimental thymic tumor model composed of thymic nurse cells and abundant lymphoid stroma. These sorted cells were examined for FOXP3 and adiponectin immunoreactivity and subsequently exposed to triple-negative breast cancer MDA-MB-157 and -231 cells. RESULTS: Adiponectin-expressing Treg were obtained by CD4- and CD25-positive sorting and cell death was induced in triple-negative breast cancer cells through the cell-in-cell phenomenon. CONCLUSIONS: Adiponectin-expressing Treg may be candidates for adoptive cell therapy against triple-negative breast cancer.

Experimental model of micronodular thymic neoplasm with lymphoid stroma.

BACKGROUND: Micronodular thymic neoplasm with lymphoid stroma (MNT), a subtype of thymic tumor, is histopathologically characterized by micronodular thymic epithelial cell nests with lymphoid stroma. Despite the distinct histopathology of MNT, its pathogenesis remains unclear. METHODS: In this study, we aimed to examine a thymic tumor harboring thymic epithelial and lymphoid cells in a nonobese diabetic/severe combined immunodeficiency mouse. RESULTS: The excised tumor cells were cultured in vitro and comprised epithelial tumor cells and lymphoid cells. During a three-dimensional cell culture, the epithelial tumor cells formed micronodular cell nests surrounded by lymphoid stroma. Notably, the lymphoid cells underwent apoptosis when they were separated from the epithelial tumor cells. Cutaneous transplantation of the cultured epithelial cells with splenocytes from BALB/c mice led to tumor formation, and these cells demonstrated a histopathology similar to that of human MNT in a nonobese diabetic/severe combined immunodeficiency mouse. CONCLUSION: Given its overlapping features with human MNT, the transplanted tumor could serve as an experimental model of this disease.

Clinical Predictors of Grade Group Upgrading for Radical Prostatectomy Specimens Compared to Those of Preoperative Needle Biopsy Specimens.

BACKGROUND: Decision-making and selection of treatment modalities for newly diagnosed prostate cancer (PCa) are often determined by risk stratification using grade group (GG), prostate-specific antigen (PSA), and clinical stage. The discrepancies between needle biopsy (NB) and radical prostatectomy (RP) specimens often occur because of the sampling errors in NB or multifocal features of PCa. Thus, we aimed to estimate the preoperative clinical factors for predicting GG upgrading after robot-assisted RP (RARP). METHODS: In this retrospective study, we reviewed the clinical and pathological records of patients who underwent RARP at Gifu University Hospital. We focused on patients with organ-confined PCa who had not received neoadjuvant therapy prior to RARP. The primary endpoint was identified as the predictive factor of GG upgrading for RARP specimens compared to those of NB specimens. RESULTS: Eighty-one patients were included in this study. The enrolled patients were divided into two groups: those who had GG upgrading for RARP specimens (the NB upgrade group) or those who did not have GG upgrading (the no upgrade group). The median age of all patients was 70 years, and the median body mass index (BMI) was 22.9 kg/m2. The median neutrophil count was 3720/µL, lymphocyte count was 1543/µL, and neutrophil-to-lymphocyte ratio (NLR) was 2.24. In univariate analysis, BMI, PSA, neutrophil count, and NLR were significantly associated with GG upgrading in RARP specimens compared to NB specimens. BMI and NLR were identified as strong predictive factors for GG upgrading in RARP specimens in the multivariate analysis. CONCLUSIONS: Although this study's small number of enrolled patients was a vital weakness, BMI and NLR might have been significantly correlated with GG upgrading for RP specimens compared with NB specimens. Therefore, BMI and NLR may have potential benefits for newly diagnosed patients with PCa in terms of decision-making and the selection of treatment modalities.

Tumor suppressor effect of an antibody on xenotransplanted sarcomatoid mesothelioma cells.

BACKGROUND: As mesothelioma generally has an unfavorable prognosis, further advances are needed to improve the outcomes in patients with mesothelioma. In the present study, we generated and characterized a monoclonal antibody that could inhibit mesothelioma cell proliferation in a xenotransplantation mouse model. METHODS: We generated monoclonal antibodies by immunizing mice with cultured mesothelioma cells. These antibodies were then characterized by immunofluorescence staining, immunohistochemical staining, secondary antibody-drug conjugate assay, antibody inoculation in a xenotransplantation mesothelioma mouse model, and mass spectrometry followed by small interfering RNA (siRNA) analysis. 5' rapid amplification of complementary DNA ends followed by sequencing was performed to deduce the amino acid sequences of the variable regions of the light and heavy chains of AX10. RESULTS: An IgG2b κ-type AX10 antibody against the cell surface membrane of sarcomatoid mesothelioma cells was generated. AX10 immunoreactivity was detected in 12 out of 22 different mesothelioma tissue specimens, but there was little AX10 immunoreactivity in a normal human tissue array. AX10 decreased Matrigel invasion by MPM-1 cells but did not affect cell proliferation. Notably, AX10 significantly inhibited the proliferation of MPM-1 cells xenotransplanted into Severe combined immunodeficiency-Nonobese diabetic mice. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry followed by siRNA silencing indicated that AX10 reacted to a unique alternatively spliced isoform of sarcolemma-associated protein. AX10 is composed of as yet unregistered amino acid sequences in its variable region. CONCLUSIONS: AX10 could have therapeutic potential for patients with sarcomatoid mesothelioma.

Gastric carcinosarcoma with FGFR2 amplification under long-term control with pazopanib: a case report and literature review.

BACKGROUND: Gastric carcinosarcoma is most frequently diagnosed at an advanced stage when the tumor is generally large with invasion into other organs, lymph node metastasis, and distant metastasis. Standard chemotherapy has not been established, and surgery is the only curative treatment. Here, we present a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. CASE PRESENTATION: A 77-year-old man was referred to our hospital because of nausea and vomiting. Computed tomography and upper gastrointestinal endoscopy revealed a type 1 tumor arising from the gastric antrum and extending into the duodenal bulb. He underwent distal gastrectomy (D2) with Roux-en-Y reconstruction. Histopathologically, the tumor had mixed adenocarcinoma and sarcoma components. According to the tumor-node-metastasis classification, the diagnosis was primary gastric carcinosarcoma pT1bN1M0 stage IB. Liver metastasis was detected 2 months after surgery; multiple lung metastases were detected 17 month after surgery. A genomic profiling test was performed using liver specimens as the patient became refractory to chemotherapy commonly used for gastric cancer, and the test revealed FGFR2 amplification along with TP53 R209*, AKT3 N127D, NOTCH1 A2036T, and POLD1 M161I. The patient was treated with pazopanib (800 mg/daily), and the tumor growth was controlled for 11 months. CONCLUSIONS: We report a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. This case suggested that pazopanib may be effective in treating gastric carcinosarcoma.

Ovarian Clear Cell Carcinoma and Mature Cystic Teratoma Transformed to PNET and Carcinosarcoma: A Case Report with an Immunohistochemical Investigation.

Ovarian tumors include neoplasms derived from somatic cells and germ cells, including teratoma. Sometimes, tumors of the somatic cell type may develop from teratoma, causing diagnostic perturbation. We experienced a case of a tumor composed of several types of tissue in the ovary with a teratoma. When findings of teratoma and somatic tumor coexist in an ovary, it is difficult to differentiate whether a somatic tumor was mixed with a teratoma or a teratoma unitarily caused transformation to a somatic cell tumor. A 72-year-old Japanese woman (gravida, 3; para, 1) presented to our hospital with severe constipation and frequent urination, and a large intrapelvic tumor was detected by computed tomography (CT). Soon after admission, ultrasonography (US) and magnetic resonance imaging (MRI) revealed a large multilocular cystic tumor on her left ovary. Based on the clinical diagnosis of ovarian cancer, she underwent a left ovariectomy, appendectomy, and partial omentectomy. We observed an ovarian tumor consisting of teratoma, primitive neuroectodermal tumor (PNET), adenocarcinoma, various types of sarcomas, and clear cell carcinoma on the H and E-stained sections. The component of clear cell carcinoma showed a nuclear positive reaction against PAX8 and napsin A, as well as a loss of ARID1A, suggesting typical endometriosis-derived clear cell carcinoma. On the other hand, the expression of ARID1A was maintained in teratoma, PNET, non-specific adenocarcinoma, and various types of sarcomas, suggesting that these tumors had an origin different from that of clear cell carcinoma. These findings indicated that the ovarian tumor of this patient contained a clear cell carcinoma derived from a somatic cell and a teratoma that transformed to a wide variety of somatic cell types of tumors, which coexisted on one ovary. The appropriate use of immunohistochemistry was diagnostically effective in this case.