[A Case of Combined Use of Endoscopic Submucosal Dissection and Transanal Excision for Early Rectal Cancer with Extension into the Anal Canal].

A 77-year-old woman visited our hospital after noticing bleeding during defecation. Lower gastrointestinal endoscopy revealed an early rectal tumor with extension into the anal canal, thus transanal excision was performed. However, histopathological examination revealed a positive surgical margin, therefore, additional transanal excision was performed with endoscopic submucosal dissection, and the residual cancer tissue was completely resected. At one year after surgery, no recurrence has been observed.

[A Case of Complete Onychomadesis after Oral UFT/LV Therapy with Long-Term Follow-Up].

A 79-year-old man underwent a radical resection for cecal cancer. The pathological diagnosis was pT4a, N1a, M0, pStage Ⅲb(Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, 9th edition). He was treated with oral UFT/LV as adjuvant chemotherapy for 6 months. At 7 months, after the end of treatment, he lost all the nail plates on his fingers and toes. A dermatologist examined him and diagnosed these as side effects of the anticancer drugs. Due to this issue, he was unable to perform routine, fine work using his fingertips. Approximately 1 year and 5 months after the completion of treatment, his nail plates regenerated to the extent that about half of his nail beds were covered. At 2 years after the completion of treatment, the nail plates began to cover the entire nail beds. Although there have been very few reports of onychomadesis as a delayed adverse event of anticancer drugs, oncologists must be aware of this possibility, as onychomadesis may impact patients' quality of life significantly.

[Decision-Making Regarding Adjuvant Therapy for Hormone Receptor-Positive, HER2-Negative Early Breast Cancer].

In December 2021, abemaciclib was approved as an adjuvant treatment for hormone receptor-positive, HER2-negative, high-risk early breast cancer in Japan. The Oncotype DX Breast Cancer Recurrence Score program(Oncotype DX)is a test that can be used to limit overtreatment in hormone receptor-positive, HER2-negative, low-risk early breast cancer. Although the target groups of both these are different and usually without many overlapping indications, we encountered a case in which this therapy and test were used in a short time period. Our experience suggests that even if the result of Oncotype DX indicates that hormone therapy alone is sufficient, it does not imply that abemaciclib is unnecessary, although this has not been directly studied in the monarchE trial. While a wider choice of treatment options is desirable for patients, more clinical data and trials are needed to further validate the utility of abemaciclib without chemotherapy.

[Hyponatremia Causing a Tonic-Clonic Seizure after Breast Cancer Surgery-The Medical Safety Perspective].

A 61-year-old woman was found to have calcifications in the CD region of the left breast. She had previously undergone total hysterectomy and bilateral oophorectomy for endometriosis at the age of 37 years. Since age 59 years, she had been attending an otorhinolaryngology clinic because of vertigo. Blood tests showed no abnormal findings. Left breast cancer (cT1N0M0, stage Ⅰ)was diagnosed, and left mastectomy and sentinel lymph node biopsy were performed. She developed postoperative nausea, and at 37 hours postoperatively, she was unable to communicate and exhibited suspected delirium. At 43 hours postoperatively a tonic-clonic seizure occurred. Hyponatremia, with serum sodium of 114 mEq/L, was present. Sodium supplementation was provided, and the patient became capable of communication 8 hours after seizure onset(Na 121 mEq/L). A hyponatremic tonic-clonic seizure is extremely rare after breast cancer surgery, and the abnormal behavior of the present patient 31 hours after surgery was also highly unusual. With such an unusual presentation, the possibility that something specific is happening must be considered. This case gave us the opportunity to review patient management after breast cancer surgery, emergency response and preparations, and nursing education from the medical safety perspective.

[Clinical Outcome of Microsatellite Instability-High Patients Treated with Pembrolizumab and Genetic Counseling].

Prospective studies have demonstrated the efficacy of pembrolizumab in patients with previously treated unresectable or metastatic microsatellite instability-high(MSI-H)cancers. Pembrolizumab has been covered by the Japanese health insurance system since December 2018. The frequency of MSI-H in patients is as low as approximately 2%. In addition, some patients with MSI-H cancers are diagnosed with Lynch syndrome. In the present study, we retrospectively investigated patients who received MSI testing at Kitasato University Hospital from April 2019 to June 2020. We also investigated the therapeutic effect of pembrolizumab for MSI-H cancers and patients who received genetic counseling for Lynch syndrome. Results identified that 5 out of 263 patients who underwent MSI testing(1.9%)had MSI-H. The therapeutic outcomes of pembrolizumab in those patients were as follows: 1(20%)complete response, 3(60%)partial response, and 1(20%) progressive disease. The positive-outcome rate of MSI-H treatment in our institution was comparable to that in the previous reports. The high response rate of pembrolizumab was confirmed in the present study. Four out of 5 patients received genetic counseling at the genetic clinic, and 1 patient underwent genetic testing for Lynch syndrome. No deleterious variant of Lynch syndrome was detected in the genetic testing.

Examination of the efficacy of olanexidine gluconate for surgical site infections in colorectal cancer elective surgery.

INTRODUCTION: The preoperative skin antiseptic, olanexidine gluconate (OLG), which has been available in Japan since 2015, is also known to be effective against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and Pseudomonas aeruginosa. This study attempted to clarify OLG efficacy against surgical site infections and antiseptic-related adverse events as compared to conventionally used povidone iodine (PVP-I). METHODS: Propensity score matching was performed on 307 patients who underwent surgery for colorectal tumors at our hospital. All 116 cases (58 PVP-I cases, 58 OLG cases) who were diagnosed with colorectal cancer were included. We examined surgical site infection rate after disinfection using PVP-I and OLG, length of hospitalization stay (days) after surgery, adverse events associated with antiseptics, and additional medical costs associated with adverse events caused by antiseptics. RESULTS: The surgical site infection rate was 8.6% in both the PVP-I and OLG groups, with no significant difference observed. The number of postoperative hospitalization days in the PVP-I group was 12.9 (±6.9) days and 16.4 (±14.6) days in the OLG group, which exhibited no significant difference (p = 0.10). Although no complications due to antiseptics were observed in the PVP-I group, skin-related side effects were observed in 8 patients (13.8%) in the OLG group. The median additional medical cost was 730 [120-1823] yen. CONCLUSIONS: OLG was as effective as the conventional PVP-I for surgical site infections during colorectal cancer elective surgery. However, significantly higher skin disorders occurred in OLG, thereby making it necessary to evaluate antiseptic use in conjunction with patient burden.

[Treatment Regimens for Breast Cancer in Elderly Patients in Whom the Diagnosis Was Switched from Malignant Phyllodes Tumor to Spindle-Cell Carcinoma after Surgery].

The patient was a 79-year-old woman with a left breast mass. Magnetic resonance imaging showed a cystic mass with a diameter of 10×8 cm and an ulcer in the upper outer quadrant and the nipple-areola region of the left breast. Intracystic carcinoma was thus suspected. A mass with a diameter of 1 cm was found in the upper outer quadrant of the right breast. Needle biopsy revealed that a cystic mass in the left breast was diagnosed as a malignant phyllodes tumor. A mass in the right breast was diagnosed as Luminal A breast cancer. The clinical tumor stage was T1N0M0. Computed tomography showed no enlarged bilateral axillary lymph nodes. In the left breast, mastectomy was performed with extensive skin excision above the tumor. In the right breast, partial mastectomy was performed with sentinel lymph node biopsy. On postoperative pathological examination, the diagnosis of left breast tumor was triple-negative spindle-cell carcinoma. The pathological tumor stage was diagnosed as T4bNxM0. Taking into consideration treatment according to breast cancer stage and age, we selected 4 courses of weekly-paclitaxel, endocrine therapy, irradiation to the left chest wall, and irradiation to the residual right breast. The preoperative diagnosis was malignant phyllodes tumor. The postoperative diagnosis was switched from malignant phyllodes tumor to spindle-cell carcinoma. It was therefore difficult to determine the presence or absence of additional resection and postoperative treatment regimens. Even though the preoperative diagnosis was a malignant phyllodes tumor, surgical procedures such as sentinel lymph-node biopsy should be considered, taking into account the possibility of breast cancer.

[A Case Report of Triple Negative Breast Cancer Diagnosed as Granulomatous Mastitis].

Granulomatous mastitis is a chronic inflammatory disease of unknown causes that forms a breast mass and may be difficult to distinguish from breast cancer on imaging studies. The patient was a woman in her 50's. Needle biopsy was performed for a mass in the upper outer quadrant of the right breast and revealed granulomatous mastitis. Breast magnetic resonance imaging showed that the tumor was malignant. Taking into account that there is a difference between histologic findings and imaging findings and that surgery after steroid therapy for granulomatous mastitis is more likely to cause complications, we decided to perform lumpectomy. The definitive pathological diagnosis was a triple negative, pT1cN0cM0 medullary carcinoma. Postoperative adjuvant chemotherapy was performed. The absence of axillary lymph-node metastasis was confirmed by right axillary sentinel lymph-node biopsy. Radiotherapy was performed on the preserved breast region. Even if granulomatous mastitis is diagnosed, biopsy should be repeated while paying attention to biopsy methods if there is a difference between pathological findings and image findings.

[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].

A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy( CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.

[A Case Report of Breast Cancer Followed Up as Intraductal Papilloma].

The patient was a 50-year-old woman. She had been diagnosed with bilateral breast tumors at another hospital 5 years previously and was followed up every 2 months. Ultrasonography showed hypoechoic masses in her breasts. The largest tumor in the right breast was 15mm in diameter and located in region A, while that in the left breast was 8mm in diameter and located in region B. Magnetic resonance imaging(MRI)showed multiple bilateral breast tumors. The largest tumor was 12mm in diameter and was suggestive of breast cancer. Core needle biopsies(CNB)of the largest tumors in both breasts were performed. Intraductal papilloma(IDP)and low-grade intraductal papillary carcinoma were diagnosed in the right and left breasts, respectively, on immunohistochemical staining. We performed left nipple-sparing mastectomy with sentinel lymph node biopsy and right tumor excision for diagnoses of carcinoma of the left breast(cTisN0M0)and IDP of the right breast. The histopathological diagnosis of the left breast tumor was pT1aN0M0, triple negative breast cancer with extensive intraductal components, and that of the right breast tumor was IDP with atypical ductal hyperplasia. Chemotherapy was administered postoperatively. Several studies have reported that peripheral IDP often coexists with or follows the development of carcinoma. Therefore, we should also closely follow-upthe patient's right breast.

[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

[Which Should be Treated First - Breast Cancer or Uterine Myoma?]

The patient was a 51-year-old woman with a mass in the left breast.At the first presentation, she had abdominal distension and liver dysfunction.Mammography showed a category 5 mass in the left breast and a category 4, unstructured region in the right breast.Pathological examination revealed bilateral, invasive ductal carcinomas.Stage II B disease(clinical T2N1M0)was diagnosed in the left breast, and Stage I disease(clinical T1N0M0)was diagnosed in the right breast.Computed tomography revealed a massive uterine myoma compressing the inferior vena cava.Liver dysfunction was suspected to be caused by these factors.Preoperative chemotherapy was scheduled to treat breast cancer.A gynecologist stated that "uterine myoma is unlikely to cause liver dysfunction" and refused to perform a hysterectomy.However, we diligently negotiated with him to avoid chemotherapy-induced venous thrombosis and pulmonary infarction; eventually, a hysterectomy(3.6 kg)was performed. After surgery, liver function was normal.Subsequently, breast cancer could be safely and adequately treated.In patients who have benign disease, as well as malignant tumors, treatment of the malignant tumors is generally given the highest priority.However, there are cases when the treatment of benign disease has priority over the treatment of malignant tumors.It is therefore important to intensively discuss such cases with physicians from other departments.

[A Case Report of Ipsilateral Nipple Skin Recurrence].

We report our experience with a patient with breast cancer who showed recurrence in the nipple skin 5 years and 10 months after a breast-preserving surgery. The patient was a woman, and was 65-years old at the time of initial surgery. Breast-preserving surgery and axillary lymph-node dissection were performed for left breast cancer. Invasive ductal carcinoma of the breast(pT3N0M0)was triple-negative, and the patient postoperatively received adjuvant chemotherapy. Left breast pain developed 5 years and 6 months after surgery. Computed tomography showed no evidence of recurrence, and the symptoms resolved after treatment with non-steroidal anti-inflammatory drugs(NSAIDs). After 3 months, however, the left nipple had enlarged to about 1.5 cm, and the surrounding skin was red and painful. Treatment with NSAIDs was thus resumed. After 1 week, redness of the nipple skin and pain were improved. However, the nipple had enlarged to twice its normal size. Nipple skin biopsy was subsequently performed, and revealed adenocarcinoma invading the skin. Left axillary lymph-node metastasis was suspected, but there was no evidence of metastasis to other sites or recurrence. Conservative total mastectomy with axillary lymph-node dissection was thus performed. The histopathological diagnosis was the recurrence of invasive ductal carcinoma, arising mainly in the reticular layer of the dermis. Chemotherapy was administered postoperatively. There has been no evidence of recurrence as of 1 year after surgery.

Phase II randomized, controlled trial of 1 day versus 3 days of dexamethasone combined with palonosetron and aprepitant to prevent nausea and vomiting in Japanese breast cancer patients receiving anthracycline-based chemotherapy.

PURPOSE: Dexamethasone, plus a 5-HT3 receptor antagonist and an NK-1 receptor antagonist are recommended for controlling the chemotherapy-induced nausea and vomiting (CINV) of highly emetogenic chemotherapy. Several days of dexamethasone are effective for CINV; however, dexamethasone also has side effects. The purpose of this trial was to investigate whether the use of a second-generation 5-HT3 receptor antagonist and an NK-1 receptor antagonist could allow a reduced dose of dexamethasone for breast cancer patients receiving highly emetogenic chemotherapy. METHODS: Eighty breast cancer patients who received an anthracycline-cyclophosphamide combination regimen were enrolled. The patients were randomized to arm A (dexamethasone days 1-3) and arm B (dexamethasone day 1). The primary endpoint was complete response (CR) (no emetic episodes and no rescue medication) during the overall phase (days 1-5). The secondary endpoints were the CR during the delayed phase (days 2-5), complete control (CC) (no emetic episodes, no rescue medication, and no more than mild nausea) during the overall phase, and the safety of this antiemetic therapy. RESULTS: There were no significant differences in the rates of CR and CC between arm A and B as follows: CR overall phase--arm A: 82.9%, 90% confidence interval [CI] 71.3-90.5% vs arm B: 82.1%, 90% CI 70.0-90.0%; p = 1.00; CR delayed phase--arm A: 87.8%, 90% CI 77.0-93.9% vs arm B: 94.9%, 90% CI 85.6-98.3%; p = 0.43; CC overall phase--arm A: 48.8%, 90% CI 36.4-61.3% vs arm B: 61.5%, 90% CI 48.4-73.2%; p = 0.27. There were very few adverse events and no severe adverse events associated with this antiemetic therapy. CONCLUSIONS: The results suggest that the antiemetic effect provided by dexamethasone administered for 3 days can be obtained by dexamethasone administered for 1 day.

[A Patient with a Pathological Complete Response to Neo-Adjuvant Chemotherapy for Triple-Negative Breast Cancer Followed by Recurrence after Six Months].

The patient was a 68-year-old woman who received neo-adjuvant chemotherapy(4 courses of weekly paclitaxel plus bevacizumab and 4 courses of 5-fluorouracil epirubicin, and cyclophosphamide)for cT1N1M0, Stage II A right-sided triplenegative breast cancer(TNBC). Right breast-conserving surgery with axillary lymph-node dissection was performed. The postoperative pathological diagnosis was a complete response. Six months after surgery, the patient developed lower and right-sided back pain. Detailed examination revealed multiple metastases to the liver, bone, lymph nodes of the mediastinum, and bile duct. The recurrence was treated with biweekly paclitaxel plus bevacizumab. The patient's pain dramatically improved. However, the duration of the response was only 3 months. The patient received eribulin as a second-line treatment, but did not respond and subsequently died. TNBC is considered to have relatively good outcomes if a pathological complete response(pCR)is obtained after preoperative chemotherapy. However, recurrence occurred after only 6months in our patient. In patients with TNBC, physical examinations and simple laboratory tests should be performed every 1 to 2 months after surgery, even if a pathological complete response is obtained. We used paclitaxel plus bevacizumab to treat recurrence of TNBC. Although this treatment did not prolong overall or disease-free survival, the patient temporarily responded, and her quality of life was maintained. Further studies are needed to elucidate the pathogenesis of TNBC and to develop more effective treatments.

The safety of concentrated trastuzumab in 100 ml of saline solution for administration to patients with HER2-positive breast cancer: a phase 1 study.

BACKGROUND: It is recommended that administration of trastuzumab should be carried out in a volume of 250 ml of saline solution over 90 min. Since 2011, recommendations have allowed a shortening of the administration time to 30 min at the second administration. However, the volume to be administered is still 250 ml. The purpose of this study was to evaluate the safety of trastuzumab administered in 100 ml of saline solution over 30 min. METHODS: This study enrolled patients with HER2-positive breast cancer. Three dose levels of trastuzumab, each in 100 ml of saline solution, were used (2, 6 and 8 mg/kg). The primary end point was the determination of safety. RESULTS: Nine patients were enrolled. Since no adverse events were observed, the 8 mg/kg/100 ml saline solution dose level was the recommended dose. CONCLUSIONS: A 30-min administration of trastuzumab in 100 ml of saline solution is safe in patients with HER2-positive breast cancer.

[A case of facial nerve palsy induced by nab-paclitaxel].

The patient was a 60-year-old woman who underwent total mastectomy and axillary lymph node dissection for right breast cancer. She was treated with adjuvant chemotherapy( epirubicin plus cyclophosphamide[EC]and paclitaxel), hormone therapy, and radiation therapy. Multiple lung, lymph node, and bone metastases were detected after 4 years. The patient subsequently received nab-paclitaxel (nabPTX, 260 mg/m2, triweekly) and zoledronate therapy. Ptosis of her right eyebrow and the right angle of her mouth were observed after 8 courses of nabPTX, and peripheral right facial nerve palsy was diagnosed. She underwent rehabilitation, and facial nerve palsy improved after 9 months. Peripheral facial nerve palsy is a very rare adverse event of nabPTX. This is the first case report of peripheral facial nerve paralysis associated with nab- PTX.

Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis.

BACKGROUND: We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). METHODS: Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. RESULTS: PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor forming and invasive ability. CONCLUSION: Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.

[Efficacy and safety of lidocaine hydrochloride jelly for the treatment of pain caused by breast cancer metastases to the skin].

Breast cancer metastases to the skin significantly decrease quality of life(QOL) due to bleeding or dull pain. However, an effective treatment has not yet been established. In this study, we achieved an effective result by using lidocaine hydrochloride jelly[Xylocaine jelly(XJ)] when patients complained of temporarily increased dull pain. For the pain treatment for 5 women who developed the skin metastases of breast cancer after mastectomy, non-steroid anti-inflammatory drugs (NSAIDs) were used. In cases with defective control, both NSAIDs and opioids were used. However, it was difficult to control temporarily increased dull pain. Therefore, we applied 5 g XJ to the area of recurrence when the patients complained of increasing dull pain. This treatment rapidly reduced the pain and it was possible to reduce the use of analgesics and reduce side effects. After 5 g XJ was applied to the patients, their level of lidocaine in blood was reduced to within the safe zone, and no undesirable effects were observed. Treatment with XJ was easy to perform and was safe for the control of dull pain due to skin metastases of breast cancer. In conclusion, we believe that treatment with XJ is effective for dull pain.

Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer.

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer. METHODS: PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status. RESULTS: PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression. CONCLUSIONS: We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.