Transcription Factor E3/Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Axis in Renal Cell Carcinoma Affects Tumor Microenvironment.

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. TFE3 is related to the PI3K/Akt pathway in RCC, and the results of this study suggest that PI3K/Akt inhibitors potentially may aid in treatment of patients with RCC by affecting the tumor microenvironment.

Clinical outcomes of esophageal granular cell tumors with different endoscopic resection methods.

Esophageal granular cell tumors (GCTs), the second most common subepithelial tumors (SETs) of the esophagus, are potentially malignant with no definite management guidelines available. We retrospectively enrolled 35 patients with endoscopically resected esophageal GCTs between December 2008 and October 2021 and evaluated the clinical outcomes from the various methods performed. Several modified endoscopic mucosal resections (EMRs) were performed for treating esophageal GCTs. Clinical and endoscopic outcomes were evaluated. Mean age of patients was 55.8 ± 8.2, with majority being men (57.1%). Mean tumor size was 7.2 ± 2.6 mm, most (80.0%) were asymptomatic and present in the distal third of the esophagus (77.1%). Endoscopic characteristics predominantly included broad-based (85.7%) and whitish-to-yellowish color changes (97.1%). Endoscopic ultrasound (EUS) of 82.9% of the tumors revealed homogeneous hypoechoic SETs originating from the submucosa. The five endoscopic treatment methods used were: ligation-assisted (77.1%), conventional (8.7%), cap-assisted (5.7%), and underwater (5.7%) EMRs and ESD (2.9%). Mean procedure time was 6.6 ± 2.1 min, and no procedure-associated complications were noted. The en-bloc and complete histologic resection rates were 100% and 94.3%, respectively. No recurrences were noted during follow-up, and no significant differences in the clinical outcomes of the different methods of endoscopic resection were found. Based on tumor characteristics and therapeutic outcomes, modified EMR methods can be effective and safe. However, there were no significant differences in the clinical outcomes of the different methods of endoscopic resection.

B7-H3 expression is associated with high PD-L1 expression in clear cell renal cell carcinoma and predicts poor prognosis.

BACKGROUND: Clear cell Renal cell carcinoma (ccRCC) is an immunogenic tumor. B7 family members, such as CTLA-4, PD-1, and PD-L1, are the main components of immune checkpoints that regulate various immune responses. Specifically, B7-H3 regulates T cell-mediated immune responses against cancer. This study aimed to analyze the association between B7-H3 and CTLA-4 expression and the prognostic factors of ccRCC to provide a basis for their potential use as predictive factors and in immunotherapy. METHODS: Formalin-fixed paraffin-embedded specimens were obtained from 244 ccRCC patients, and B7-H3, CTLA-4, and PD-L1 expressions were evaluated using immunohistochemical staining. RESULTS: B7-H3 and CTLA-4 were positive in 73 (29.9%) and 57 (23.4%) of the 244 patients, respectively. B7-H3 expression was significantly associated with PD-L1 expression (P <  0.0001); however, CTLA-4 expression was not (P = 0.842). Kaplan-Meier analysis showed that positive B7-H3 expression was associated with poor progression-free survival (PFS) (P <  0.0001), whereas CTLA-4 expression was not (P = 0.457). Multivariate analysis revealed that B7-H3 was correlated with poor PFS (P = 0.031), whereas CTLA-4 was not (P = 0.173). CONCLUSIONS: To the best of our knowledge, this study is the first to investigate B7-H3 and PD-L1 expression and survival in ccRCC. B7-H3 expression is an independent prognostic factor for ccRCC. Furthermore, multiple immune cell inhibitory targets, such as B7-H3 and PD-L1, can be used for therapeutic tumor regression in a clinical setting.

Mycobacterium intracellulare Tenosynovitis with Rice Body Formation with Literature Review.

Rice body formation is a rare response to chronic inflammation of the synovial membrane. It is most commonly associated with rheumatoid arthritis and tuberculosis. Recently, there have been reports of rice bodies caused by non-tuberculous mycobacterial infection. We describe a case of rice body formation in a 69-year-old man who presented with pain and swelling in his third finger for six months after being punctured by a wire 1 year ago. He had no other notable recent medical history. Magnetic resonance imaging showed a large amount of fluid collection with diffuse thickening and enhancement of the synovium and rice bodies along the flexor tendon of the third finger. During surgery, multiple granular white rice bodies were found from the third carpal bone to the distal phalanx. Mycobacterium intracellulare was identified through mycobacterial culture and the patient was treated with rifampin, ethambutol, and clarithromycin, without recurrence. This case reveals that Mycobacterium intracellulare infection can cause tenosynovitis with rice bodies.

DNA Extracted from Cytologic Slides Is a Valuable Source for PCR-Based Molecular Tests.

INTRODUCTION: DNA extracted from cytologic samples is occasionally used for various molecular tests. The aim of this study was to evaluate DNA extracted from differently prepared cytologic slides that can be used for PCR-based molecular tests. METHODS: For each 23 cases of papillary thyroid carcinoma or colorectal adenocarcinoma tissues, six touch-imprinted cytological slides were prepared (group 1∼3), and remnant tissues were blocked for FFPE tissue (group 4). Cytologic slides were grouped by preparation methods: air-dried slides (group 1), fixed slides (group 2), and stained slides (group 3). Fixed slides were classified as 95% ethanol fixed (group 2A) and CytoRich Red Preservative solution fixed (group 2B). Stained slides were divided in 3 ways: Giemsa, Pap, and H&E stained (group 3A, 3B, and 3C, respectively). DNA extracted from each group was evaluated for concentration, 260/280 ratio, DNA Integrity Number (DIN) value, and mutation. RESULTS: DNA concentration was highest in group 1 and lowest in group 2B. DIN value was highest in group 2A and lowest in group 2B. A mutation of BRAF or KRAS genes was detected in 18 FFPE tissue samples. Matched DNA extracts from groups 1, 2A, and 3 produced results consistent with FFPE tissue results, while mutation testing was successful for only four samples of DNA from group 2B. CONCLUSION: The mutation tests worked well for most samples except CytoRich Red Preservative-fixed slides. This study indicates that stained and unstained cytologic slides are a suitable source of PCR-based molecular tests as long as they are fixed in ethanol or stored for a short time in an air-dried condition.

Combination conventional endoscopy and endoscopic ultrasound can differentiate between esophageal granular cell tumors and leiomyomas.

Esophageal leiomyomas and granular cell tumors (GCTs) are the 2 most common subepithelial tumors found in the esophagus. We attempted to differentiate the 2 tumors using endoscopic findings and endoscopic ultrasound (EUS) features. Between December 2008 and June 2021, a total of 38 esophageal GCTs and 11 esophageal leiomyomas originating from the muscularis mucosa were selected. Clinical characteristics and endoscopic features were retrospectively reviewed. Although esophageal GCTs are mainly located in the lower third of the esophagus (81.6%), esophageal leiomyomas are mainly located in the upper third of the esophagus (45.5%). Broad-based (84.2%, P = .002) and whitish-to-yellowish color changes (97.4%, P < .001) are significant endoscopic features of esophageal GCTs. The echogenicity of esophageal leiomyoma was similar to that of proper muscle echogenicity. However, the echogenicity of esophageal GCTs was hyperechoic compared to that of the proper muscle layer (90.0% vs 9.1%, respectively, P < .001). EUS revealed a clearer hyperechoic epithelial lining in the esophageal leiomyoma than in esophageal GCTs (100% vs 26.7%, respectively, P < .001). The 5 endoscopic factors (location of the lower third, broad base, whitish-to-yellowish color, hyper-echogenic, and unclear demarcated hyperechoic epithelial line) were counted to differentiate esophageal GCTs from esophageal leiomyomas. Tumors with 3 or more endoscopic factors were all esophageal GCTs. The characteristic endoscopic and EUS features of esophageal GCTs were broad-based, whitish-to-yellowish colored subepithelial tumors located in the lower third of the esophagus and hyperechoic tumor with an unclear demarcated hyperechoic epithelial line. A combination of these features can predict esophageal GCTs before endoscopic resection.

NOL4 is a novel nuclear marker of small cell carcinoma and other neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) such as small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have characteristic histologies, but immunohistochemistry using neuroendocrine markers is still desirable to confirm diagnosis. CD56 is the most sensitive marker, but also stains various normal tissues and other tumors. Recently, we reported that nucleolar protein 4 (NOL4) is present in the blood of SCLC patients and found it was stained in the SCLC nuclei. In this study, we compared expressions of NOL4 and CD56, using 64 cases of SCLC, 18 cases of LCNEC, 6 cases of atypical carcinoid tumor, 7 cases of typical carcinoid tumor, 68 cases of lung adenocarcinoma, and 62 cases of lung squamous cell carcinoma. For primary lung NENs, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of NOL4 were 77.5%, 95.8%, 93.2%, and 85.1%, respectively, while those of CD56 were 92.1%, 93.3%, 91.1%, and 94.1%. The specificity and PPV of NOL4 were higher than those of CD56, although the differences were not statistically significant. However, NOL4 retains its nuclear immunoreactivity in areas of crush artifact or necrosis. Furthermore, NOL4 was not expressed in adjacent normal tissues including bronchial cells and pneumocytes. Therefore, a combination of NOL4 staining with other cytoplasmic or membranous neuroendocrine markers might enhance diagnostic utility for SCLC and other NENs.

Primary testicular carcinoid tumor with marked lymphovascular invasion.

Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.

mTOR Inhibition Increases Transcription Factor E3 (TFE3) Activity and Modulates Programmed Death-Ligand 1 (PD-L1) Expression in Translocation Renal Cell Carcinoma.

The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell-intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.

Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations.

BACKGROUND: The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). CASE PRESENTATION: A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for 1 week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G > T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G > A/p.E542K in exon 10). CONCLUSIONS: We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.

Primary pleural liposarcoma combined spindle cell lipoma of the lung.

Liposarcoma is a malignant adipose tissue tumor which mainly originates from the extremities and retroperitoneum. Primary pleural liposarcoma is very rare. Spindle cell lipoma is a rare benign adipose tissue tumor. A 66-year-old male was referred to our hospital for the evaluation of a mass-like opacity visible on chest X-ray. Computed tomography (CT) scan revealed a well-defined soft tissue mass with internal low attenuations and adjacent multiple nodules in the upper lobe of the left lung, and surgical excision was subsequently performed. Histopathological findings revealed adipose tissue with lipoblasts and spindle cells and immunohistochemical staining (IHC) revealed the tumor cells were strongly positive for CDK4 and MDM2. Histopathological examination of the small lung nodules showed spindle cell proliferation and adipose tissue without positivity for MDM2. Here, we report a rare case of primary pleural liposarcoma combined adjacent spindle cell lipoma of the lung.

Gastric-type gene expression and phenotype in non-terminal respiratory unit type adenocarcinoma of the lung with invasive mucinous adenocarcinoma morphology.

AIMS: We sought to determine if non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. METHODS AND RESULTS: We reviewed whole-section images of 489 cases of lung adenocarcinoma from The Cancer Genome Atlas (TCGA). TCGA data were classified into 426 TRU type adenocarcinoma, 49 IMA and 14 unclassifiable. Their RNA sequencing data was analysed by DESeq2 and WGCNA R packages. Gene expression in patients' samples was measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10 was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes, including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2 and VSIGI, was increased> 15-fold in IMA. Immunohistochemistry of ANXA10, TFF2 and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed a predominant expression in IMA, but are not in TRU type adenocarcinoma. CONCLUSION: Our results showed the level of genes expressed in stomach mucosa was increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help the understanding of the pathogenesis of IMA and discovery of therapeutic targets.

TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis.

AIMS: Since Xp11.2 translocation-associated renal cell carcinoma (TRCC) was first recognised, its morphological features and the clinical significance of TFE3 expression, frequency of gene translocation and diagnostic criteria have been the subject of limited studies. The present retrospective analysis aimed to evaluate the correlation between TFE3 immunoreactivity and its gene translocation status using fluorescence in-situ hybridisation (FISH) and determine how TFE3 translocation and expression affect patient prognosis differently. METHODS AND RESULTS: We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE3 was performed in 303 cases, and FISH analysis was performed for molecular testing. The TCGA data set of renal cell carcinoma was evaluated to validate TFE3 expression and survival analysis. TFE3 expression was associated significantly with the nested alveolar pattern, papillary pattern, eosinophilic cytoplasm, voluminous expansile cytoplasm, nuclear grade, tumour necrosis, sarcomatoid pattern and picket fence appearance. FISH analysis showed break-apart signals in 26 of 32 (81.25%) cases expressing strong or moderate nuclear TFE3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE3 expression with morphologically suspicious cases were translocation-positive in the FISH assay. The TFE3-translocation group (harbouring TFE3 translocation regardless of TFE3 expression) showed the poorest progression-free survival (PFS), and the TFE3-expressing group (expressing TFE3 but negative for translocation) was correlated significantly with decreased PFS. CONCLUSION: Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.

A peculiar case report of extraovarian Brenner tumor arising in the omentum.

BACKGROUND: Brenner tumors almost always develop in the ovary. Exceptionally, extraovarian Brenner tumors have been reported in the lower abdomen or pelvic organs. Here, we introduce a peculiar case of an extraovarian Brenner tumor arising in the omentum. CASE PRESENTATION: A 43-year-old woman presented with a palpable abdominal mass. Computed tomography (CT) scan revealed a 9.0-cm solid mass in the omentum. The tumor was not associated with pelvic structures, including the ovaries. It was excised under the clinical impression of an extragastrointestinal stromal tumor or neurogenic tumor. Grossly, the mass was a well-circumscribed solid tumor, with yellow-tan cut surface and minute cystic spaces. Microscopically, the tumor showed well-defined epithelial nests with variable cystic changes embedded in an abundant fibrous stroma. The cells within the nests were reminiscent of benign urothelial cells in that they had oval, frequently grooved nuclei. The epithelial cells focally showed a gradual transition into the surrounding stromal cells with short spindled features. The urothelium-like cells were positive for pancytokeratin, WT-1, p63, CK7, uroplakin-III, and GATA-3 but were negative for CD34, CD10, CK20, c-KIT, DOG-1, PAX-8, and calretinin. Morphological and immunohistochemical features of the tumor were the same as an ovarian Brenner tumor, and so it was diagnosed as an extraovarian Brenner tumor. CONCLUSIONS: Although the location of the tumor was very unusual, we could diagnose the tumor as an extraovarian Brenner tumor on the basis of the histologic and immunohistochemical findings. This is the first case of extraovarian Brenner tumor arising in the omentum near the stomach ever reported in the English literature.

Gastrointestinal tract spindle cell tumors with interstitial cells of Cajal: Prevalence excluding gastrointestinal stromal tumors.

Leiomyomas and schwannomas of the gastrointestinal tract (GIT) are mainly comprised of spindle-shaped tumor cells and should always be differentiated from gastrointestinal stromal tumors (GISTs). Mast/stem cell growth factor receptor Kit (KIT) and discovered on GIST-1 (DOG1) are well-known diagnostic markers for the detection of a GIST by immunohistochemical staining. The aim of the present study was to assess the prevalence and significance of spindle cell tumors of the GIT with KIT- or DOG1-positive spindle-shaped cells, presumed to be interstitial cells of Cajal (ICCs), other than GISTs. A total of 71 leiomyomas and 35 schwannomas were examined and clinicopathological information was obtained. KIT and DOG1 immunostaining was performed to determine the proportions of positive cells. Mutation screening of KIT exons 9, 11, 13 and 17, and platelet-derived growth factor receptor α (PDGFRA) exons 12 and 18 was performed in cases with a relatively high proportion of either KIT- or DOG1-positive cells. The frequency of leiomyomas and schwannomas with KIT- and DOG1-positive ICCs was 35.2% (25/71 cases) and 5.7% (2/35 cases), respectively. Among the esophageal leiomyomas with KIT- and DOG-positive ICCs (14/25; 56.0%), 5 leiomyomas involved the muscularis mucosa and 9 leiomyomas involved the muscularis propria. All gastric leiomyomas with KIT- and DOG1-positive ICCs (11/25; 44%) involved the muscularis propria. All schwannomas with an increased proportion of KIT- or DOG1-positive ICCs were of gastric origin. No KIT or PDGFRA mutations were detected in 7 leiomyomas and 2 schwannomas. In conclusion, the majority of leiomyomas and the minority of schwannomas in the GIT had a significant portion of KIT- and DOG1-positive cells. All of the tumors were located in the upper GIT, and could be present in the muscularis propria or muscularis mucosa. The tumors represented a non-neoplastic proliferation of KIT- and DOG1-positive cells in the GIT. Careful evaluation of KIT- or DOG1-positive cells in spindle cell tumors of the GIT can assist in forming the correct diagnosis by differentiation from a GIST.

Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component.

AIM: To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment. METHODS: We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components. RESULTS: LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not. CONCLUSION: We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.