Reporting hormone receptor expression in breast carcinomas: which method has the highest prognostic power and what should be the optimal cut-off value?

Background . Hormone receptor (HR) expression is a critical marker that plays a role in the treatment and management of breast cancer. Even if patients receive hormone treatment with a hormone positivity rate of over 1%, it is controversial at what level of positivity they benefit from treatment and contribute positively to their prognosis. Methods . We retrospectively examined the estrogen receptor (ER) / progesterone receptor (PR) expression status, clinicopathological findings, and survival data of 386 patients who underwent surgery for breast cancer. ER/PR expressions of the patients were evaluated according to Allred, H-score and were also grouped according to staining percentages. Separate cut-off values were determined for each of these evaluation methods, and the prognostic power of these methods was investigated using receiver operating characteristic analysis. Results . The prognostic power of all methods was found to be similar in terms of predicting survival. According to the staining percentage of the patients, survival was excellent if the ER value was >80% and the PR value was >1%. Conclusions . All recommended methods for reporting HRs have similar prognostic power. However, in patients with high percentage staining for ER using these methods, the prognosis is excellent. As a result, we predict that if the percentage of ER staining is low, changing the treatment management of patients may be considered clinically

Apoptotik indeks meme kanserli hastalarda neoadjuvan kemoterapiye yanıtı predikte eder mi?

Objective: Neoadjuvant chemotherapy (NACT) plays a major role in the treatment of patients with locally advanced breast carcinoma. Although most patients have benefited from NACT, the rate of residual tumors is still high after treatment (AT). An increase in apoptosis is expected in tru-cut biopsy (TCB) during treatment or AT as the mechanism of NACT is inducing apoptosis. This study aimed to investigate whether evaluating the apoptotic index (AI) from TCB can predict the response before treatment (TC-BT) and whether there is a correlation between AI and clinicopathologic parameters. Methods: Seventy cases of breast carcinomas were included. The AI was evaluated BT and AT by quantifying the apoptosis. The receiver operating characteristic analysis was performed with overall survival (OS) data, and low and high AI cut-offs were obtained. The relationship between AI and response and clinicopathological parameters was evaluated. Results: A significant relationship was found between low AI in TC-BT and at least partial response (p=0.025), longer OS (p=0.01) and disease-free survival (p=0.01), and progesterone receptor-positive tumors (p=0.03). Her2-negative tumors were more prone to low AI. A significant decline in AI (p=0.001) and Ki67 proliferation index (p[removed

Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer

OBJECTIVE: Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. METHODS: In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated.RESULTS: A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. CONCLUSION: Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy

myomterial invazyon paterninin prognostik önemi: Retrospektif bir çalışma

Objective: Endometrioid endometrial carcinomas (EEC) are the most commonly diagnosed malignancies of the female genital tract. Myometrial invasion depth is one of the most significant pathological prognostic parameters. Different morphological invasion patterns have been characterized. This study aimed to investigate the prognostic significance of the microcystic elongated and fragmented (MELF) myometrium invasion pattern in patients with EEC and its relationship with other clinicopathological parameters. Methods: This study included 101 patients with EEC in our institution between 2011 and 2020. The MELF pattern was evaluated in hematoxylineosin-stained sections. Pan-cytokeratin staining was performed on paraffin-embedded blocks of lymph nodes for cases without lymph node metastasis. Results: The MELF pattern was observed in 29 (29.8%) patients. It was significantly associated with lymphovascular invasion (p<0.001), pathologic stage (p=0.048), infiltrative pattern (p<0.001), and necrosis (p=0.005). No significant correlation was observed between the MELF pattern and overall and disease-free survival rates. Conclusions: The MELF pattern is associated with other prognostic parameters, but its prognostic significance for survival has not been found. If the MELF pattern is observed in the hysterectomy material for cases without lymph node dissection during the first surgery, these patients may need additional surgery or adjuvant therapy due to the high risk of lymphovascular invasion and lymph node metastasisAmaç: Endometrioid endometriyal karsinomlar (EEK) kadın genital sistemin en sık karşılaşılan maligniteleridir. Myometrium invazyon derinliği en önemli patolojik prognostik parametrelerden birisidir. Farklı morfolojik invazyon paternleri tanımlanmıştır. Biz çalışmamızda EEk olgularında mikrokistik elonge fragmante (MELF) myometirum invazyon paterninin prognostik önemini ve klinikopatolojik parametrelerle ilişkisini araştırmayı amaçladık. Yöntemler: 2011-2020 yılları arasında kurumumuzda EEK tanısı alan 101 hasta çalışmaya dahil edildi. Hematoksilen eozin kesitlerde MELF paterni değerlendirildi. Lenf nodu metastazı izlenmeyen olgularda lenf nodu bloklarına pan-sitokeratin uygulandı. Bulgular: Yirmi dokuz hastada (%29,8) MELF paterni izlendi. MELF paterni lenfovasküler invazyon (p<0,001), patolojik evre (p=0,048), infiltratif patern (p<0,001), ve nekroz (p=0,005) ile anlamlı ilişkili izlendi. Genel ve hastalıksız sağkalımda MELF paterni istatistiksel olarak anlamlı ilişkili izlenmedi. Sonuçlar: MELF paterni diğer prognostik parametrelerle ilişkili olup tek başına prognostik önemi saptanmamıştır. Ancak ilk cerrahi sırasında lenf nodu diseksiyonu yapılmayan EEK hastalarında histerektomi materyalinde MELF paterni saptanması durumunda yüksek lenfovasküler invazyon ve lenf nodu metastaz riski nedeniyle ek cerrahi işlem ya da adjuvan terapi kararında MELF paterni varlığının dikkate alınması gerektiğine inanıyoruz

Nucleolus assessment in invasive breast carcinoma, an objective parameter for histological grading

Background/aim: The nucleolus has the potential to provide insight into how many types of cancer will progress. In this study, we examined the evaluation of the nucleolus with a microscope in widespread breast cancer tumors and whether this value contributes to tumor grading as an objective clinicopathological parameter. Materials and methods: In our study, the nucleolus was evaluated retrospectively in resections with a diagnosis of invasive breast carcinoma of the cases between January 2010 and April 2021. In total, the tumor nucleolus of 377 cases of invasive breast carcinoma was evaluated. Nucleolus evaluation was performed with light microscopy using four different modes (modified Helpap method, in 1, 5, and 10 high power fields at 40x magnification). The relationship between nucleolar scores and clinicopathological parameters was examined separately. Regrading was performed by replacing nuclear pleomorphism with the nucleolar score in the classically used histological grading system and utilizing the nucleolus score as the fourth parameter in this grading system. Results: There was no significant correlation between the prognosis of the patients and the nucleolar score. When nuclear pleomorphism and nucleolar score were replaced in the classical grading system, disease-free and overall survival were correlated with the new grading system. In addition, a relationship was found between high nucleolus score and other clinicopathological parameters (such as estrogen receptor negativity, progesterone receptor negativity, high Ki-67, triple negative, and human epidermal growth factor receptor-2 status). Conclusion: The presence of nucleolus is associated with disease-free survival and overall survival of patients, and it can be evaluated with a light microscope at no extra cost and time. Therefore, in the classical grading, using it instead of nuclear pleomorphism with low reproducibility among pathologists may provide more objective results in predicting patient prognosis

A new practical method of estimating tumoral microenvironment parameters of possible prognostic significance in patients with invasive breast carcinoma: Combined microenvironment score

Background and objective: In recent years, the tumor microenvironment has become increasingly recognized as an influential factor in breast cancer development and growth. The parameters that form the microenvironment are the tumor stroma ratio and tumor infiltrating lymphocytes. In addition, tumor budding, which shows the ability of the tumor to metastasize, gives information about the progression of the tumor. In this study, the combined microenvironment score (CMS) was determined with these parameters, and the relationship between CMS and prognostic parameters and survival was evaluated.Materials and methods: In our study, tumor stroma ratio, tumor infiltrating lymphocytes, and tumor budding were evaluated in hematoxylin-eosin sections of 419 patients with invasive ductal carcinoma. Patients were scored separately for each of these parameters, and these scores were summed to determine the CMS. The patients were divided into 3 groups according to CMS and the relationship between CMS and prognostic parameters and the survival of the patients was studied.Results: The patients with CMS 3 had higher histological grade and Ki67 proliferation index compared to CMS and 2. Additionally, lymphovascular invasion, axillary lymph node and distant metastasis were more common. Disease-free, and overall survival were significantly shortened in the CMS 3 group. CMS was found as an in-dependent risk factor for DFS (HR: 2.144 (95 % CI: 1.219-3.77) p: 0.008), but not an independent risk factor for OS.Conclusion: CMS is a prognostic parameter that can be easily evaluated and does not require extra time and cost. Evaluating the morphological parameters of the microenvironment with a single scoring system will contribute to routine pathology practice and predict patient prognosis

Tumor budding is an independent prognostic factor to predict overall survival in endometrial endometrioid carcinoma: A retrospective study

Objective. Tumor budding defined as a tumor cell nest away from the main tumor, has been found to be associated with prognostic parameters in many cancer types. We aimed to investigate the relationship between tumor budding and clinicopathological parameters in endometrioid endometrial carcinomas, as well as its prognostic importance. Materials and Methods. One hundred four patients who underwent surgical resection with diagnosis of endometrioid endometrial carcinomas between June 2011 and May 2020 were included. The area where tumor budding was the most prominent was determined, and tumor budding was counted from hematoxylin and eosin-stained section at one high power field (X 200). By performing ROC analysis, the cut off value was obtained in order to divide the patients into low and high tumor budding groups. Results. The cut off value was determined as 1/0.95 mm(2) according to the ROC analysis. Tumor budding was observed in 24 (23%) patients. Tumor budding significantly associated with poor overall survival (P < .001), distant metastasis (P = .001), presence of angiolymphatic invasion (P < .001), lymph node metastasis (P = .024), cervical invasion (P < .001), high FIGO grade (P < .001), large tumor size (P = .004). In multivarate analysis, tumor budding and age were found to be an independent risk factor for overall survival (P = .003, P = .014 respectively). Conclusion. Tumor budding is a significant morphological parameter independent of other prognostic parameters in endometrioid endometrial carcinomas. Standardizing the assesment and scoring of tumor budding, as well as including this entity in routine pathology reports could light the way for ideas in the risk analysis of patients

The effects of amiodarone in ovarian injury due to oxidative stress and inflammation caused by ischemia-reperfusion

Objective Ovarian ischemia constitutes 2-3% of all gynecological emergencies. New-generation therapeutic agents need to be discovered, in addition to invasive interventions capable of reducing the risk of potential ovarian ischemia to a minimum and protecting against potential adverse outcomes. Aims To investigate the effects of amiodarone (AMD) on ischemia-reperfusion-induced oxidative stress and inflammation-induced ovarian damage. Methods The control group, received intraperitoneal (i.p.) injection of saline solution. The ischemia group (I-Group), was subjected to ischemia-induced injury without drug administration. The ischemia + AMD (50 mg/kg) group was subjected to ischemia injury and also received i.p. 50 mg/kg AMD prior to induction of ovarian ischemia. The ischemia-reperfusion (I/R group) was exposed to ischemia and reperfusion-induced injury without drug administration. The I/R + AMD (50 mg/kg) group underwent I/R injury together with i.p. administration of 50 mg/kg AMD prior to induction of ovarian I/R. The Sham + AMD group received intraperitoneal (i.p.) injection of 50 mg/kg AMD alone. In this study performed thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin 1 Beta (IL-1 beta), interleukin 6 (IL-6), toll-like receptor 4 (TLR4) and nuclear factor-kappa B(NF-kappa beta). Results Increased oxidative stress and inflammation as a result of ovarian I and I/R application activated the cascade. AMD was not sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-k beta, which were up-regulated by triggering oxidative stress and inflammation, were not regressed by the effects of AMD. Conclusions AMD, used as an antiarrhythmic agent, was found to be insufficient, despite its antioxidant and anti-inflammatory properties, to reduce the experimentally induced ovarian tissue damage

The effects of vitamin B12 on the TLR-4/NF-κB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factor kappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1β (IL-1β) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1β, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue

The protective effects of trimetazidine against ovary ischemia-reperfusion injury via the TLR4/Nf-kB signal pathway

Late diagnosis and treatment of ovarian ischemia can lead to worsening of ischemia, irreversible damage to ovarian functions and infertility. In this process, there is no approved medical treatment that can reduce the negative effects of ischemia and contribute positively to ovarian functions during reperfusion after detorsion. Rats were randomly assigned into one of six groups of eight animals each. The groups were designed as follows: The control group, The ischemia(I) group, The Ischemia + Trimetazidine (I + TMZ) (20 mg/kg) group, and The ischemia-reperfusion group (I/R). The Ischemia-Reperfusion + Trimetazidine (I/R + TMZ) (20 mg/kg) group, and The Sham + Trimetazidine (Sham + TMZ) (20 mg/kg) group. In this study performed thiobarbituric acid reactive substances (TBARS), total thiol (-SH), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), toll-like receptor 4 (TLR4), and nuclear factor-kappa B(NF-kappa beta). Increased oxidative stress and inflammation were as a result of ovarian I and I/R application. Trimetazidine (TMZ), was sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-kappa beta, which were upregulated by oxidative stress and inflammation, were regressed by TMZ. TMZ should be considered as a potential therapeutic agent in addition to surgery in the clinical treatment of ovarian torsion