PURPOSE: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway has a central role in regulation of cell proliferation, differentiation, motility and survival. This pathway has recently generated great interest because its elements are, potentially, novel targets for the treatment of various malignancies, including breast cancer. METHODS: Using tissue microarray sections of breast carcinoma, we performed immunohistochemical studies using antibodies against the phosphorylated forms of Akt (p-Akt) and mTOR (p-mTOR) in 530 invasive breast carcinomas and 30 ductal carcinomas in situ (DCIS). We investigated possible associations between expression of these proteins and clinicopathologic characteristics and disease outcomes. RESULTS: In 530 invasive carcinomas, weak and strong expression of p-Akt was observed in 180 (34.0%) and 288 (54.3%) cases, respectively. The expression of p-Akt was associated with expression of estrogen receptors (ER) (p=0.045), progesterone receptors (PR) (p=0.003), lymph node metastasis (p<0.001) and cancer stage (p=0.027). Weak and strong expression of p-mTOR was found in 136 (25.7%) and 207 (39.1%) cases, respectively. The mTOR pathway was more frequently activated in DCIS than in invasive breast carcinoma (p=0.001). p-mTOR expression was associated with expression of ER (p=0.040), PR (p=0.009), tumor size (p<0.001), and stage (p=0.002). In a univariate analysis, strong expression of p-Akt was associated with longer disease-free survival (DFS). In a multivariate analysis, neither p-Akt nor p-mTOR was associated with DFS. CONCLUSION: The PI3K/Akt/mTOR pathway is active in DCIS as well as in invasive carcinoma of the breast. Our study also suggests that the PI3K/Akt/mTOR pathway is influenced by ER rather than erbB-2, and that this pathway may contribute more to cancer pathogenesis in ER-positive tumors.
Antibodies ; Breast ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Cell Proliferation ; Disease-Free Survival ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Phosphatidylinositol 3-Kinase ; Proteins ; Receptors, Estrogen ; Receptors, Progesterone ; Sirolimus ; TOR Serine-Threonine Kinases

Two dogs presented with bilateral pattern-forming corneal opacity. Treatment with topical immunosuppressants was initiated after a complete ophthalmic examination. The response to treatment was assessed by analyzing serial images using slit-lamp biomicroscopy and spectral domain optical coherence tomography (SD-OCT). Both dogs responded to topical immunosuppressants; however, the lesions recurred once the treatment was abated or withdrawn. The most effective immunosuppressant in both dogs was 0.03% tacrolimus ointment. Early and continuous treatment with topical immunosuppressants may be necessary to improve corneal clarity and prevent scarring. SD-OCT could provide useful structural information regarding presumed immune-mediated keratitis and aid in monitoring treatment response.

Background: Long-term comparative data of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco-ECP) versus phacoemulsification (phaco) alone in dogs are rare. Objectives: To investigate the effects of ECP on postoperative intraocular pressure (IOP) and complications after phaco in dogs with normal IOP. Methods: Medical records of IOP, conjunctival hyperemia, corneal edema, aqueous flare, posterior synechia, intraocular fibrin, and posterior capsule opacification (PCO) formation in 15 canine eyes that underwent phaco-ECP and 36 eyes that underwent phaco alone were evaluated retrospectively. ECP was applied when either the iridocorneal angle or the ciliary cleft was narrow or closed. Results: The IOP of the phaco-ECP group persisted within the normal range postoperatively.The phaco-ECP group had a shorter period of dorzolamide use than did the phaco group.PCO was formed earlier in the phaco-ECP group than in the phaco group. The phaco-ECP group showed more severe corneal edema than the phaco group at every follow-up visit.Posterior synechia was more severe in the phaco-ECP group than in the phaco group from two weeks until the last follow-up. Conclusions Although ECP might cause more postoperative complications such as corneal edema and posterior synechia, it could effectively reduce the incidence of IOP increase after phaco in dogs with a high risk of postoperative glaucoma.

Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.

BACKGROUND: Mycobacterial culture is the gold standard test for diagnosing tuberculosis (TB), but it is time-consuming. Polymerase chain reaction (PCR) is a highly sensitive and specific method that can reduce the time required for diagnosis. The diagnostic efficacy of PCR differs, so this study determined the actual sensitivity of TB-PCR in tissue specimens. METHODS: We retrospectively reviewed 574 cases. The results of the nested PCR of the IS6110 gene, mycobacterial culture, TB-specific antigen-induced interferon-γ release assay (IGRA), acid-fast bacilli (AFB) staining, and histological findings were evaluated. RESULTS: The positivity rates were 17.6% for PCR, 3.3% for the AFB stain, 22.2% for mycobacterial culture, and 55.4% for IGRA. PCR had a low sensitivity (51.1%) and a high specificity (86.3%) based on the culture results of other studies. The sensitivity was higher (65.5%) in cases with necrotizing granuloma but showed the highest sensitivity (66.7%) in those with necrosis only. The concordance rate between the methods indicated that PCR was the best method compared to mycobacterial culture, and the concordance rate increased for the methods using positive result for PCR or histologic features. CONCLUSIONS: PCR of tissue specimens is a good alternative to detect tuberculosis, but it may not be as sensitive as previously suggested. Its reliability may also be influenced by some histological features. Our data showed a higher sensitivity when specimens contained necrosis, which indicated that only specimens with necrosis should be used for PCR to detect tuberculosis.
Diagnosis* ; Granuloma ; Methods ; Necrosis ; Polymerase Chain Reaction* ; Retrospective Studies ; Sensitivity and Specificity ; Tuberculosis*

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Neuroendocrine ; Carcinoma, Squamous Cell ; Chemotherapy, Adjuvant ; Cholecystectomy ; Drug Therapy ; Female ; Follow-Up Studies ; Gallbladder Neoplasms ; Gallbladder ; Humans ; Liver ; Middle Aged ; Neoplasm Metastasis ; Prognosis

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. METHODS: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. RESULTS: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. CONCLUSIONS: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

No abstract available.
Humans ; Recurrence

This study was aimed to evaluate the prophylactic anti-glaucoma effect of topical 5% betaxolol (BTX) and 2% dorzolamide (DRZ) on the second eye in dogs with unilateral primary angle closure glaucoma (PACG). Medical records of 60 dogs with unilateral PACG who received prophylactic anti-glaucoma eyedrops in the second eye, from 2016 to 2021, were reviewed. The duration of prophylactic effects of BTX only and DRZ after BTX failure was calculated. The prophylactic effects of BTX were maintained on 28/60 (46.7%) eyes until last visit and BTX failure was observed on median 510 (range, 53-1,927) days in 32/60 (53.3%) eyes. After DRZ instillation in BTX failure eyes, the prophylactic effects were extended at median 610 (range, 157-2,270) days in 21/32 (65.6%) eyes. DRZ failure eyes (17/21, 81.0%) eyes required chemical ablation or surgical intervention due to uncontrolled intraocular pressure. The duration of prophylactic effects was decreased with aging (R² = 0.334, p = 0.006). The predominant breeds were Shih-Tzu (41.9%) and American Cocker Spaniel (30.6%) with no significant differences in survival curves (p = 0.210). The average prophylactic effects of BTX persisted more than 1.5 year and could be selected the first prophylactic eye drop in unilateral PACG. Also, early surgical intervention should be considered in prophylactic medications failure cases.

No abstract available.
Adenocarcinoma ; Thymoma