PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer: a retrospective study.

BACKGROUND: Fluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. METHODS: We analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates. RESULTS: We detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher's exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1. CONCLUSIONS: The two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.

Vimentin-positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics.

Vimentin is a stable mesenchymal immunohistochemical marker and is widely recognized as a major marker of mesenchymal tumors. The purpose of the present study was to investigate if the vimentin expression status might serve as a significant predictor of outcomes in patients with invasive breast carcinoma of no special type (IBC-NST) and to investigate, by comprehensive RNA sequencing analyses, the mechanisms involved in the heightened malignant potential of vimentin-positive IBC-NSTs. This study, conducted using the data of 855 patients with IBC-NST, clearly identified vimentin expression status as a very important independent biological parameter for accurately predicting the outcomes in patients with IBC-NST. RNA sequence analyses clearly demonstrated significant upregulation of coding RNAs known to be closely associated with cell proliferation or cellular senescence, and significant downregulation of coding RNAs known to be closely associated with transmembrane transport in vimentin-positive IBC-NSTs. We conclude that vimentin-positive IBC-NSTs show heightened malignant biological characteristics, possibly attributable to the upregulation of RNAs closely associated with proliferative activity and cellular senescence, and downregulation of RNAs closely associated with transmembrane transport in IBC-NSTs.

Evaluation of Thymidylate Synthase Expression in Prostate Cancer.

Thymidylate synthase (TS), a key enzyme in DNA synthesis, is over-expressed in a variety of cancer cells. 5-Fluorouracil, an anticancer agent clinically used against various cancers, including prostate cancer, inhibits DNA synthesis by binding TS. In this study, we investigated expression of TS in prostate cancer and its prognostic significance. Seventy-five prostatic tissue specimens were obtained from patients who had undergone prostate biopsy for diagnosis of prostate cancer. We analyzed the cancerous tissue specimens for TS expression using immunohistochemistry. TS expression was significantly increased in patients with bone metastasis. No relationship was found between expression of TS and the other clinicopathological findings. Because TS expression could be used as a prognostic parameter in patients with prostate cancer, an accurate prediction of prognosis might help to select patients for more intensive surgical, hormonal, or chemotherapeutic approaches, including 5-fluorouracil. Additional prospective studies are warranted to define the role of TS in selecting patients for adjuvant therapy for prostate cancer.

Primary signet-ring cell carcinoma of the lung: a report of 2 cases.

BACKGROUND: Signet-ring cell carcinoma is a distinct subtype of mucin-producing adenocarcinoma that originates in various organs, particularly the stomach. However, primary signet-ring cell carcinoma of the lung is an extremely rare condition. The preoperative identification of signet-ring cells by cytologic examination is vital because signet-ring cell carcinoma of the lung has been reported to have a worse prognosis than ordinary adenocarcinoma. In this study, we present 2 cases of primary signet-ring cell carcinoma of the lung in conjunction with their cytomorphologic features. CASES: Bronchial brush and wash samples were obtained from the lungs of a 63-year-old woman and a 65-year-old man for the evaluation of lung tumors. Examination of the bronchial samples revealed many large clusters of atypical cells containing abundant intracytoplasmic mucin. Although the clusters were equivocal in the first case, the presence of more atypical cell clusters led to the diagnosis of adenocarcinoma. CONCLUSION: Signet-ring cell carcinoma should be considered when many atypical round cells with abundant intracytoplasmic mucin--namely, signet-ring cells--are observed along with adenocarcinomatous cells.

Radiology contributes to better cytological diagnosis of lung tumors.

OBJECTIVES: Cytology is well established and widely accepted method to diagnose lung tumors. However, cytological changes of malignant cells can be so subtle that cytopathologists cannot always diagnose with certainty. In such cases, some cytopathologists believe that radiological assessment is important for correct cytological diagnosis. However others deny the importance of radiological information, because they believe it could not change the cytological assessment. This study mainly aimed to clarify how radiologist's comments affect cytological diagnosis of lung tumors. METHODS: Of 201 patients who underwent cytological examinations, 131 and 57 patients were diagnosed with malignant and benign lung lesions, respectively. Study coordinators randomly selected 60 cytological slides each of the benign and malignant lesions. A radiologist graded their CT images by using a 5-point confidence scale. Three cytotechnologists assessed the 120 cytological slides twice on the basis of a 5-grade classification: first before and then after obtaining radiologist's grading. Receiver operating characteristic analysis was performed. The Az values, sensitivities, and specificities of the cytological diagnoses were calculated for comparing the results before and after obtaining radiologist's grading. RESULTS: The mean Az value for cytological assessment after obtaining radiologist's grading (0.88) was significantly higher than that before obtaining radiologist's grading (0.78). The mean sensitivity of cytological assessment after obtaining radiologist's grading (77%) was significantly higher than that before obtaining radiologist's grading (67%). CONCLUSIONS: Radiological assessment, together with a radiologist's confidence, improves cytological diagnoses of lung diseases. Thus, the importance to positively provide radiological assessment to cytopathologists should be considered by all clinicians.