Which factors help to determine the long-term response to first-line tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma: A Turkish multi-centre study.

Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder's group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. For patients in the favourable risk group, the lack of brain metastasis was a predictor of long-term response. In the intermediate-poor risk group, prior nephrectomy and ECOG PS <1 were predictive factors for long-term response. Some individuals with mRCC may experience a durable response to TKIs. The likelihood of a long-term response can be determined by factors such as nephrectomy, ECOG PS < 1, and the absence of brain metastases.

Evaluation of the relationship between Ki67 expression level and neoadjuvant treatment response and prognosis in breast cancer based on the Neo-Bioscore staging system.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is widely used in the treatment of primary breast cancer. Different staging systems have been developed to evaluate the residual tumor after NAC and classify patients into different prognostic groups. Ki67, a proliferation marker, has been shown to be useful in predicting treatment response and prognosis. We aimed to investigate the prognostic importance Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels in breast cancer patients who received NAC and correlations between Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels. METHODS: A total of 176 invasive breast carcinoma patients who underwent NAC were included in the study. Ki67 levels were evaluated by immunohistochemical methods in Trucut biopsy and surgical excision specimens. Patients were classified into prognostic groups using the Neo-Bioscore staging system. RESULTS: Patients with high pretreatment Ki67 score were more likely to be in the higher Neo-Bioscore risk group (p < 0.001). Patients with a high posttreatment Ki67 score were more likely to be in the higher Neo-Bioscore prognostic risk group (p < 0.001). Overall survival (OS) and disease-free survival (DFS) were shorter in patients with high posttreatment Ki67 scores and in patients in the higher Neo-Bioscore risk group. We also determined a cutoff 37% for pathological complete response. CONCLUSION: Neo-Bioscore staging system is found to be important in predicting survival. The posttreatment Ki67 level is more important than pretreatment Ki67 level in predicting survival.

A case of castration-resistant metastatic prostate cancer who continued treatment with enzalutamide after epileptic seizure.

INTRODUCTION: Enzalutamide is an androgen receptor inhibitor and is used in metastatic castration-resistant prostate cancer. Seizure is a rare side effect of enzalutamide. In this case, the patient had an epileptic seizure while on enzalutamide treatment. His treatment management and and use of enzalutamide afterwards is discussed. CASE REPORT: A 78-year-old male patient who received previous treatments for metastatic castration-resistant prostate cancer was started on enzalutamide due to progression, and had an epileptic seizure while taking enzalutamide was presented. Different pathologies such as the use of other drugs, brain metastasis, bleeding, electrolyte, liver and kidney disorders that can cause epileptic seizures were explored and not found to be the cause in this patient. No neurological pathology was found in the patient after the seizure. MANAGEMENT AND OUTCOME: Enzalutamide and antiepileptic treatment were initiated simultaneously again in the patient whose treatment was interrupted after the seizure and no pathology was found in the brain magnetic resonance imaging. Under this dual treatment, the patient did not have seizures again. DISCUSSION: Although observed rarely, enzalutamide-induced epileptic seizure is a known side effect. However, a review of literature did not reveal any report on patients for whom enzalutamide and antiepileptic treatment were initiated and followed up simultaneously after seizures. This case report will contribute to the literature for patients whose treatment options have been exhausted and who may benefit significantly from continued use of enzalutamide despite having a seizure.

Prospective evaluation of hematological parameters in preoperative renal cell cancer patients.

BACKGROUND: Of all the genitourinary cancers, renal cell carcinoma (RCC) is still the most common malignancy with high mortality rates. There are still insufficient biomarkers to predict disease prognosis. Systemic inflammation markers play an important role in tumor development and growth. There are studies which show the relationship of fibrinogen and albumin individually with cancer prognosis in many cancers. Fibrinogen/albumin ratio(FAR), on the other hand, has prognostic importance like other inflammation indicators in cancer. Therefore, we investigated whether FAR had a potential value in evaluating the prognosis of patients with nonmetastatic kidney cancer or not. METHODS: A total of 72 patients who had nephrectomy operation at 19 Mayis University, Faculty of Medicine between January 2019 and January 2021 and who did not have distant metastasis were included in the study. FAR was calculated from the blood taken from the patients before the nephrectomy operation. The cut-off value was found for this FAR by receiver operating characteristic(ROC) curve analysis. The patients were divided into 2 groups as high- and low-FAR according to this cut-off value. Kaplan Meier test was used to evaluate the predictive value of clinicopathological parameters for overall survival (OS). The Log-rank test was used to determine whether there was a relationship between the preoperative FAR and the clinico-pathological data of the patients. RESULTS: The best cutoff value for the FAR was 0.114. A FAR > 0.114 was associated with higher Fuhrman Grade (FG) (P < 0.0001) and later pathological T stage (P < 0.0001). Patients with a high FAR (> 0.114) had worse OS [Std. Error 2.932, 95% confidence interval (CI): 73.659-85.154, P < 0.0001]. In addition, a positive significant correlation was found between high grade and platelet lymphocyte ratio (p < 0,020). Furthermore, a significant correlation was found between the pathology t stage of the patients and the platelet lymphocyte ratio (p: 0.020). CONCLUSIONS: The preoperative FAR is an independent prognostic factor of OS in renal cancer patients. A FAR > 0.114 was significantly related to decreased survival in renal cancer patients. In addition, the platelet-lymphocyte ratio seems to be related to OS, as well as FAR. Further studies are required on this subject.

Oscillometric evaluation of the effects of cardiotoxic chemotherapeutic agents on vascular stiffness.

AIM: Several clinical studies have demonstrated that arterial stiffness is an early indicator of cardiovascular events. Our study aimed to detect the potential cardiovascular changes using arterial stiffness parameters and compare these changes with echocardiographic aortic stiffness parameters, in cancer patients treated with cardiotoxic chemotherapeutics. METHODS AND RESULTS: Our study is a prospective case-control study. A total of seventy subjects between the ages of 18 and 50 years were included into our study. Thirty of them were newly diagnosed cancer patients and forty constituted the age- and sex-matched control group. Baseline oscillometric arterial and echocardiographic aortic stiffness parameters were measured in all patients. In cancer patients, all of these parameters were measured again, 1 month after chemotherapy protocol was completed. Mean age of the cancer patients was 41.4 ± 5.9 years and mean age of the control group was 39.6 ± 6.6 years (P = 0.258). Before chemotherapy, arterial and aortic stiffness parameters were similar between the study and the control group. After chemotherapy, the oscillometric pulse wave velocity parameter increased compared with the control group and to the prechemotherapy values (P = 0.004 and P < 0.001, respectively). After chemotherapy, the augmentation index parameter increased compared with the control group (P = 0.013). On the other hand, no difference was detected between the groups in terms of echocardiographic aortic stiffness parameters. CONCLUSION: In newly diagnosed cancer patients treated with cardiotoxic chemotherapeutics, considerable impairment occurs in some of the oscillometric arterial stiffness parameters, while there is no substantial effect on echocardiographic aortic stiffness. Arterial stiffness parameters in these patients might be useful in evaluating subclinical cardiovascular damage.

Prognostic significance of hemoglobin-to-red cell distribution width ratio in patients with metastatic renal cancer.

The aim of the current research was to investigate the prognostic significance of pretreatment hemoglobin-to-red cell distribution width ratio (HRR) in patients with renal cell carcinoma (RCC). The neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio (LMR) and HRR were analyzed retrospectively to assess their prognostic value using Kaplan-Meier curves and Cox regression analysis in 198 patients with RCC. High HRR (0.72) and high LMR (2.43) were found to be associated with longer progression-free survival and overall survival. A multivariate analysis identified International Metastatic Renal Cell Carcinoma Database Consortium prognostic score, tumor stage, node stage, LMR and HRR as independent prognostic factors for progression-free survival, as well as International Metastatic Renal Cell Carcinoma Database Consortium score, neutrophil-to-lymphocyte ratio and HRR for overall survival. HRR is a an independent prognostic parameter predicting the progression and survival of patients with RCC.

Lay abstract Hemoglobin-to-red cell distribution width ratio (HRR) may be associated with lifespan in patients with cancer, as shown in previous studies of solid organ malignancy. The present study investigates the prognostic significance of pretreatment HRR in patients with renal cell carcinoma. A higher HRR was associated with longer survival in the present study, indicating the value of HRR as a predictor of survival and prognosis in renal cancer.

Predictive Significance of Ki-67 and Platelet Lymphocyte Ratio in Patients with Gastric Cancer Receiving Neoadjuvant FLOT Chemotherapy.

OBJECTIVE: We aimed to determine the predictive significance of Ki-67 and platelet lymphocyte ratio (PLR) in patients with gastric cancer (GC), who received fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) as neoadjuvant chemotherapy (NAC). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Faculty of Medicine,  Ondokuz Mayis University, Samsun, Turkey from March 2016 to January 2020. METHODOLOGY: Seventy-five patients with GC, who received FLOT treatment as NAC were included in the study. Ki-67 and PLR, which were examined pre-NAC and aft-NAC, were recorded. Associations between clinical-histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analysed using Kaplan-Meier curves. Cox-regression analysis was used to assess their prognostic values. RESULTS: There was a statistically significant difference between pre-NAC and aft-NAC Ki-67, and aft-NAC PLR values between groups with complete response, partial response, and stable disease aft-NAC (p: 0.023, p: <0.001; and p: 0.001, respectively). When the patients were grouped according to the pre-NAC and aft-NAC Ki-67 changes, a significant difference was found in terms of OS (p< 0.001). High pre-NAC and high aft-NAC Ki-67 were associated with shorter DFS and OS (p: 0.042, p: 0.049; p: 0.027, and p: 0.001, respectively). The high pre-NAC PLR was associated with shorter OS, while the high aft-NAC PLR was associated with shorter DFS (p: 0.018, and  p: 0.001, respectively). In multivariate analysis, aft-NAC Ki-67 was found to be an independent prognostic factor for OS. CONCLUSION: Ki-67 and PLR have predictive significance in GC patients treated with neoadjuvant FLOT. Ki-67 is an independent prognostic marker for OS in gastric cancer. Key Words: FLOT, Gastric cancer, Ki-67, Platelet lymphocyte ratio.

Sigmoid Sinus Thrombosis Followed by Splenic Infarction Due to Imatinib Therapy in a Patient with Gastrointestinal Stromal Tumor; Hematological Side Effects of Imatinib.

Imatinib has an important place as an adjuvant therapy as well as in the treatment of metastatic disease caused by gastrointestinal stromal tumor (GIST), which is one of the common mesenchymal tumors of the gastrointestinal tract. Imatinib is a tyrosine kinase inhibitor and is generally well tolerated. However, it can cause some serious adverse effects. The most common of these are edema on the face and legs, headache, fatigue, nausea, vomiting, and rash on the skin. The most serious side effects, albeit less common, are gastrointestinal or intraabdominal bleeding. However, thrombotic events such as sigmoid sinus thrombosis and splenic infarction are extremely rare. The current report presents a patient with GIST who is treated with imatinib 400 mg/day. The patient presented with edema on the face and headache in the second month of imatinib therapy, after which she was diagnosed with sigmoid sinus thrombosis. The patient who presented with abdominal pain approximately three months later developed splenic infarction. She was administered acetylsalicylic acid, supplemental oxygen (O2) in the first episode of thrombosis, and imatinib therapy was discontinued. The patient's complaints and thrombus regressed, after which imatinib therapy was resumed. She was administered intravenous hydration, supplemental oxygen, analgesics, and imatinib therapy was discontinued after the patient sustained splenic infarction. After resolution of sigmoid sinus thrombosis and the regression of splenic infarction area, the patient was switched to sunitinib therapy. She is attending routine control visits. Sigmoid sinus thrombosis and splenic infarction should be kept in mind as a rare cause of headache and abdominal pain in patients treated with imatinib, and detailed neurological and gastrointestinal evaluation should be performed.

Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study.

BACKGROUND: Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown. METHODS: A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL. RESULTS: Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42-0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39-0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms. CONCLUSIONS: Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).

[Aggressive skin metastasis in lung cancer]. / Akciger kanserinde nadir görülen yaygin cilt metastazi.

A fifty seven year old male patient was admitted to our clinic because of complaints of cough and sputum. Computed tomography revealed by a 36x25 mm mass on the lateral of the 7th left rib, a 50x52 mm mass on the right main bronchus, growing 40x34 mm lymph nodes on the carina and paratracheal, 60x42 mm mass on the right adrenal and extensive bone metastasis. Squamous cell carcinoma was diagnosed by performed bronchoscopic biopsy. Scalp dermal biopsy was taken upon detection of extensive lesions on the skin.Scalp biopsy was reported squamous cell carcinoma infiltration.The last time when was given radiotherapy to footwell metastasis, the patient was fever and hypotension, we were accepted intensive care unit. In this article, we aimed to discuss rarely aggressive skin metastasis in a squamous cell carcinoma, a type of lung cancerin the light of current literature data.

Early Response to Everolimus Therapy Detected on 68Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor.

Everolimus is a mammalian target of rapamycin inhibitor that has been recently approved for the treatment of patients with advanced progressive pancreatic neuroendocrine tumor. Here, we present a case in which an early therapy response to everolimus was effectively demonstrated by Ga-DOTATATE PET/CT.

Epithelial membrane protein 1 expression in ovarian serous tumors.

The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.

Antithyroid peroxidase antibody positivity is associated with lower incidence of metastasis in breast cancer.

Thyroid extracts were first used to treat patients with metastatic breast cancer over a century ago. Since then, a number of studies have investigated the association between thyroid disorders and breast cancer. The presence of antibodies to thyroid peroxidase (TPOab) was recently reported to be associated with improved outcome in these patients. The aim of the present study was to evaluate the association between TPOab positivity and clinicopathological characteristics in breast cancer patients. The study included 318 newly diagnosed cases of breast cancer treated at Ondokuz Mayis University Hospital, Samsun, Turkey, between 2008 and 2012. Serum thyroid-stimulating hormone, free triiodothyronine and free thyroxine levels were measured at the time of diagnosis. Of the 318 patients, 253 were considered to be TPOab-negative (TPOab ≤34 IU/ml) and 65 TPOab-positive (TPOab >34 IU/ml). No cases with distant metastases were found in the TPOab-positive group. However, 20 (7.9%) of the 253 patients displayed distant metastases in the TPOab-negative group (P=0.01). Therefore, TPOab positivity was found to be associated with a lower incidence of metastasis in breast cancer patients.

Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies.

PURPOSE: Colorectal cancer (CRC) survivors are currently living longer due to better therapies but they also need to maintain their quality of life (QoL). QoL is increasingly being used as primary outcome measure in clinical studies. This study was designed to gain knowledge about QoL during chemotherapy across different lines and different regimens. METHODS: The study comprised 101 CRC out patients receiving chemotherapy who completed the EORTC QLQ-C30 questionnaire. The Shapiro-Wilk, Kruskal-Wallis, and Mann-Whitney U tests were used for statistical analyses. RESULTS: The demographics of the patients were evaluated for QoL. Prior surgery, prior radiotherapy, working status, stage, comorbidity and sex had no effect on global health status in CRC patients, although some other demographics such as education, monthly income, age and type of chemotherapy regimen did have an effect on global health status. Role functioning was worse in older than in younger ones (p<0.05). Adjuvant chemotherapy did not affect the QoL scores negatively but palliative chemotherapy negatively affected the cognitive function, appetite loss and nausea/vomiting scores (p<0.05). According to chemotherapy regimen, the best QoL was observed with adjuvant FUFA regimen. In the palliative setting FOLFOX/Bevacizumab was associated with the best QoL scores whereas FOLFIRI/Cetuximab were associated with the worst QoL scores. CONCLUSIONS: Palliative chemotherapy maintained QoL irrespective of the chemotherapy line in metastatic CRC (mCRC) patients. Some demographics affect QoL and different chemotherapy regimens showed different QoL scores.

The value of red blood cell distribution width in endometrial cancer.

BACKGROUND: Red cell distribution width (RDW) is a routinely examined parameter with the complete blood count. In recent studies, RDW levels have been associated with cardiovascular, liver and renal diseases and solid tumors. The aim of this study was to evaluate the alterations of RDW levels in benign and malignant causes of postmenopausal bleeding and to investigate the association of RDW levels with clinicopathological parameters of endometrial cancer (EC) patients. METHODS: A retrospective study was made of a total of 884 females who were admitted to hospital for postmenopausal bleeding between May 2009 and December 2013. After inclusion and exclusion criteria were applied, 222 patients remained. Complete blood count data was obtained from the recorded computerized database. After pathological evaluation, the patients were divided into two groups, benign and malignant (EC). RESULTS: The EC group (n=113) had significantly higher RDW levels compared to the benign group (14.78±2.02 vs. 13.88±1.05; p=0.000). Grade II and above EC patients had higher levels of RDW than Grade I patients (15.2±2.3 vs. 14.1±1.00; p=0.005). Correlation analyses also revealed a negative correlation between RDW and hemoglobin levels (p=0.000), RDW and mean corpuscular volume (p=0.000), RDW and lymphocyte count (p=0.035) but a positive correlation between RDW and platelet to lymphocyte ratio (p=0.030). CONCLUSIONS: The results of the current study revealed the potential predicitve role of RDW in patients with postmenopausal bleeding. Significant associations were also determined between RDW and clinicopathological characteristics in EC patients.

Elevated serum neutrophil to lymphocyte and platelet to lymphocyte ratios could be useful in lung cancer diagnosis.

BACKGROUND: Lung cancer (LC) is still the primary cause of cancer deaths worldwide, and late diagnosis is a major obstacle to improving lung cancer outcomes. Recently, elevated preoperative or pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) detected in peripheral blood were identified as independent prognostic factors associated with poor survival with various cancers, including colon cancer, esophageal cancer, gastric cancer and breast cancer. OBJECTIVE: The aim of this study was to examine whether MPV, NLR and PLR could be useful inflammatory markers to differentiate lung cancer patients from healthy controls. An investigation was also made of the relationship between these markers and other prognostic factors and histopathological subgroups. MATERIALS AND METHODS: Retrospectively eighty-one lung cancer patients and 81 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. The preoperative or pretreatment blood count data was obtained from the recorded computerized database. RESULTS: NLR and PLR values were significantly higher in the LC patients compared to the healthy subjects.( NLR: 4.42 vs 2.45 p=0.001, PLR: 245.1 vs 148.2 p=0.002) MPV values were similar in both groups (7.7 vs 7.8). No statistically significant relationship was determined between these markers (MPV, NLR and PLR) and histopathological subgroups and TNM stages. CONCLUSIONS: NLR and PLR can be useful biomarkers in LC patients before treatment. Larger prospective studies are required to confirm these findings.

Expression of Plakophilins (PKP1, PKP2, and PKP3) in breast cancers.

UNLABELLED: Plakophilins (PKP) are desmosomal plague proteins, which belong to the p120ctn subfamily of armadillo repeat containing proteins. We aimed to analyze the role of plakophilins in breast cancer and its clinical progress. We have performed immunohistochemical study of the PKP1,2,3 in breast carcinoma. The study included 108 patients with breast cancer and 26 age- and sex-matched healthy controls. We investigated the associations between staining intensity and some clinicopathologic features like tumor size, axillary node status, stage, lymphovascular invasion, perineural invasion, grade, hormone receptor status, and c-erb B2. The mean age of patients was 46 years (22-78). In breast cancer, compared with normal tissue, PKP1 and PKP2 expressions were indifferent (P > 0.05), but PKP3 expression was significantly increased in breast cancer (P = 0.0014). Although PKP1 and PKP2 expression levels were not correlated with clinicopathological parameters, increased PKP3 expression was positively correlated with node positivity and grade (P = 0.000, P = 0.000). CONCLUSION: Overexpressed PKP3 is likely to be an essential contributor to a growth-promoting pathway and to aggressive features of breast cancer.

Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast.

Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.

Expression of plakophilins (PKP1, PKP2, and PKP3) in gastric cancers.

BACKGROUND: The importance of cell-cell junction proteins (including armadillo proteins) in tumor biology is known, but limited with regard to plakophilins. We explored the relationship between plakophilins (PKP1, PKP2, PKP3) to gastric cancer via immunohistochemical techniques. METHODS: We compared the immunohistochemistry of PKPs in 34 gastric adenocarcinomas and 20 normal gastric tissues. RESULTS: In gastric cancer, PKP1 expression was unchanged but PKP2 and PKP3 were significantly decreased as compared to normal controls. There was no observable clinical association with PKP1 or PKP2 expression; however, low PKP3 level and poor prognosis appeared to correlate with regards to node number and tumor stage. The mean disease-free survival (DFS) was 38 ± 3 months (range: 32 - 44) and mean overall survival (OS) 42 ± 4 months (range: 38 - 50). Decreased PKP2 appeared to negatively impact DFS. CONCLUSION: Decreased PKP2 and PKP3 may be early prognostic markers and loss of PKP3 expression during gastric carcinoma progression may indicate an invasive phenotype.