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 1 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 independent 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.

The prognostic significance of non-lymphoid immune cells of the tumor microenvironment, including neutrophils, eosinophils, and mast cells in breast carcinomas.

BACKGROUND AND OBJECTIVE: The prognostic importance of lymphoid cells in the tumor microenvironment and their effect on treatment response have been demonstrated in many cancer types. However, there are limited studies on non-lymphoid immune cells. Conflicting results have been obtained regarding the effects of these cells on prognosis. MATERIALS AND METHODS: A total of 331 patients who underwent surgery for breast cancer were included. Patients that received neoadjuvant chemotherapy and those with distant metastasis were excluded. CD 15 immunohistochemistry was performed to detect tumor-infiltrating neutrophils (TINs) and eosinophils (TIEs), while Toluidine Blue histochemistry was performed to detect tumor-infiltrating mast cells (TIMs). RESULTS: High TINs were statistically associated with low ER expression (p < 0.001), low PR expression (p = 0.001), high Ki-67 proliferation index (p = 0.008), and HER2/TN molecular subtypes (p = 0.001). High TIEs were associated with low ER expression (p = 0.001), high Ki67 proliferation index (p = 0.005), and HER2/TN molecular subtype (p = 0.002). High TIMs were associated with high PR expression (p = 0.024), low Ki-67 proliferation index (p = 0.003), and high survival rate (p = 0.006). TIMs and TIEs were good prognostic factors for overall survival in Luminal A and Luminal B subtypes, while TINs and TIEs were found to be independent risk factors for disease-free survival. CONCLUSION: The evaluation of components of the tumor microenvironment including TINs, TIEs, and TIMs is easy and practical. High TIMs and TIEs are independent prognostic factors, especially in luminal molecular subtype of invasive breast carcinoma. However, to use this parameter in routine pathology practice, more studies from different centers and standard evaluation are needed.

Tumor-infiltrating lymphocytes (TILs)/volume and prognosis: The value of TILs for survival in HER2 and TN breast cancer patients treated with chemotherapy.

BACKGROUND AND OBJECTIVE: The use of the tumor microenvironment as a target in creating treatment modalities and as a biomarker in predicting treatment response has become increasingly important. Tumor-infiltrating lymphocytes (TILs), located in the tumor microenvironment, are the fundamental elements of the specific immunological response against tumor cells and have prognostic importance in many types of cancer. MATERIALS AND METHODS: Between January 2010 and June 2021, 350 patients who were operated on in our hospital and met the study criteria were included in the study. TILs and tumor-infiltrating lymphocyte volume (TILV) were evaluated in hematoxylin-eosin sections of the patients. RESULTS: Presence of high stromal TILs was associated with improved survival (p = 0.036), distant metastasis (p = 0.009), high nuclear and histological grade (p < 0.001), estrogen receptor (ER) and progesterone receptor (PR) negativity (p < 0.001), high Ki-67 proliferation index (<0.001), HER2 expression (p = 0.026) level, perineural invasion (p = 0.048), adjuvant chemotherapy (p = 0.005) and radiotherapy (p = 0.055) treatment. High TILV was associated with high nuclear and histological grade (p < 0.001), ER and PR negativity (p < 0.001), HER2 positivity (p = 0.013), high Ki-67 proliferation index (p = 0.001) and high tumor size (p = 0.0011). There was no significant relationship between survival (p = 0.343), distant metastasis (p = 0.632), lymph node metastasis (p = 0.141) and sTIL volume. CONCLUSION: TILs are an indicator of an anti-tumor immune response, and tumor suppressor efficiency is increased by chemotherapy and immunotherapy treatments. It is one of the factors that determine the success of the treatment. The tumor-infiltrating lymphocyte is an important parameter that can help determine the patient groups to be treated with chemotherapy, prevent unnecessary complications, and be quickly evaluated in all laboratories without any expense.

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

BACKGROUND: 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. 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). DISCUSSION: 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.

Reporting Hormone Receptor Expression in Breast Carcinomas: Which Method has the Highest Prognostic Power and What Should be the Optimal Cut-off Value?

.: 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. .: 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. .: 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%. .: 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.

Exploring the association of ADAM17 expression with survival in patients with non-small cell lung cancer.

The A disintegrin and metalloprotease (ADAM) family is involved in many vital cellular events, from proliferation to migration, and accumulated evidence suggests its increased expression in malignant tumors. In this study, we investigated ADAM17 expression in non-small cell lung cancer (NSCLC) and its relationship with clinicopathological factors and survival. Immunohistochemical staining of ADAM expression was performed in 108 patients with NSCLC and in 54 control cases with no known malignant diagnosis. Association between ADAM17 expression, clinicopathological factors, and survival were analyzed. The Kaplan-Meier method was used for survival analysis. ADAM17 was lowly expressed in 89 (82.4%) and highly expressed in 19 (17.6%) of the patients with NSCLC. In univariate analysis, high ADAM17 expression, lymphovascular invasion, stage, and treatment response significantly affected progression-free survival (PFS) and overall survival (OS) (p < 0.05). Multivariate analysis also showed that high ADAM17 expression, lymphovascular invasion, stage, and treatment response were important prognostic factors for PFS and OS (p < 0.05). Our study revealed that high ADAM17 expression significantly associated with OS and PFS in patients with NSCLC. ADAM17 may potentially be the area of a new targeted treatment strategy in NSCLC. Thus, routine evaluation of ADAM17 expression in patients with NSCLC may be a future consideration.

High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients.

OBJECTIVE: The mortality incidence of endometrial carcinomas (ECs) has increased in recent years. Therefore, recent studies have focused on the cellular and microenvironmental properties of ECs. Tumor-infiltrating lymphocytes (TILs), a component of the microenvironment, have been found to be associated with the prognosis in many tumors. Although TILs were mostly evaluated by immunohistochemical studies in ECs, in our study, the evaluation was done with a light microscope as a practical approach, and we aimed to determine the prognostic importance of TILs in endometrioid ECs. MATERIAL AND METHOD: 104 patients were included in the study. TILs in the stromal area (sTILs) were evaluated on hematoxylin and eosin (HE) stained-sections at X200 objective. The presence of TILs was evaluated as follows; 0-10% as low, 20-40% as moderate, and 50-90% as intense. Then TILs were grouped as low and high. RESULTS: Tumors with high TILs were more prone to have FIGO (International Federation of Gynecology and Obstetrics) grade 1 tumors, low nuclear grade, early pathological stage, smaller size, no lymphovascular invasion, myometrial invasion below 50%, and no cervical involvement. In the presence of high TILs, the overall survival showed significant increase but no significant correlation was found with disease-free survival. CONCLUSION: Interest in the molecular properties of ECs has increased in recent years. TIL, which can be easily evaluated in HE sections, is an important parameter in patient selection for molecular tests and determining the prognosis of patients.

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 mm2 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.

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.

Does the number of cell forming tumor budding alter the prognostic value in invasive ductal carcinoma of breast?

BACKGROUND AND OBJECTIVE: The most commonly used definition for tumor budding (TB) is a single or a cell cluster of tumor cells up to 4 cells. However, there are different opinions regarding the number of cell (NOC) forming TB. It has been proven that TB is associated with poor prognostic factors in most tumors. The current study, it was aimed to investigate the prognostic value of NOC forming TB in invasive ductal carcinoma of the breast. MATERIALS AND METHODS: 326 cases with the diagnosis of invasive ductal carcinoma were examined. The NOC forming TB was counted from hematoxylin and eosin stained slide under X200 magnification for each case, and scoring five different TB as 1, ≤ 2, ≤ 3, ≤ 4, ≤ 5, respectively. Receiver operating characteristic (ROC) analysis based on survival was performed for each TB value separately, and the cut-off was determined. RESULTS: All TB values were associated with poor outcome (p < 0.001), presence of distant metastasis (p < 0.001), high Ki67 proliferation index (p < 0.05), advanced stage (p < 0.05), presence of lymphovascular invasion (p < 0.001), and metastatic axillary lymph node (p < 0.001). According to ROC analysis performed to compare the predictiveness of survival, the area under the curve was similar for all TB values. CONCLUSION: TB was associated with poor prognostic parameters, and the prognostic value of TB was not affected by NOC forming TB. The NOC up to 4 cells which have been accepted for colon carcinomas, could also provide practicality in breast carcinomas.

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 factorkappa 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-1ß (IL-1ß) 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-1ß, 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.

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

SUMMARY 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.