Prognostic Impact of Tumor-Associated Macrophages on Long-Term Oncologic Outcomes in Colorectal Cancer.

This study evaluated the correlation between tumor-associated macrophages (TAMs) and long-term oncologic outcomes in colorectal cancer (CRC). We evaluated TAMs based on the expression of CD68, CD11c, and CD163 as optimal markers via immunohistochemistry in 148 patients with CRC who underwent surgical resection between September 1999 and August 2004. A high proportion of CD68-positive macrophages were associated with the occurrence of distant metastasis. A low proportion of CD11c-positive macrophages were associated with unfavorable overall survival (OS) and disease-free survival. CD11c-positive macrophages were found to act as independent prognostic factors for OS. An analysis of our long-term data indicated that TAMs are significantly associated with OS and prognosis in CRC.

Tumor-Associated Macrophages as Potential Prognostic Biomarkers of Invasive Breast Cancer.

PURPOSE: Tumor-associated macrophages (TAMs) are activated macrophages associated with tumor progression in various cancers. TAMs can polarize M1 or M2 type. M1 has a pro-inflammatory function and kills pathogens. Conversely, M2 shows immunosuppressive action and promotes tumor growth. There are various markers of TAMs. CD11c is considered as a specific marker of M1. CD163 is an optimal marker for M2. CD68 is known as a pan-macrophage marker. We evaluated the relationship between the clinicopathological parameters and immunohistochemical expressions of CD11c, CD163, and CD68 in invasive breast cancer (IBC), and the prognostic value of macrophage localization within the tumor stroma (TS) and tumor nest (TN). METHODS: Immunohistochemistry of CD68, CD11c, and CD163 was analyzed on tissue microarrays of 367 IBCs. The number of CD68+, CD11c+, or CD163+ macrophages in TN vs. TS was counted by 2 pathologists. The correlations between the degree of macrophage (CD68+, CD11c+, or CD163+) infiltration and the clinicopathological parameters were analyzed. We also assessed the impact of macrophages (CD68+, CD11c+, or CD163+) on disease free survival (DFS) and overall survival (OS). RESULTS: High numbers of macrophages (CD68+, CD11c+, or CD163+) were associated with higher histologic grade, higher Ki-67 proliferating index, estrogen receptor negativity, and progesterone receptor negativity. High numbers of macrophages (CD11c+ or CD163+) in TS were associated with a larger tumor size. Furthermore, CD163+ macrophages in TN were an independent prognostic marker of reduced OS and DFS. Conversely, CD11c+ macrophages in TS were an independent prognostic marker for higher OS and DFS. CONCLUSION: TAMs, including M2 type, are associated with tumor progression in IBC. They can also act as a significant unfavorable or favorable prognostic factor. In addition to simply analyzing the degree of TAM infiltration, it is also important to analyze the location of TAMs.

High RNA-binding Motif Protein 3 Expression Is Associated with Improved Clinical Outcomes in Invasive Breast Cancer.

PURPOSE: Expression of RNA-binding motif protein 3 (RBM3) is induced by hypoxia and hypothermia. Recently, high expression of RBM3 was reported to be associated with a good prognosis in colon cancer, prostate cancer, ovarian cancer, and malignant melanoma. Studies on RBM3 in invasive breast carcinoma (IBC), however, are limited. METHODS: RBM3 expression was examined using a tissue microarray from 361 patients with IBC. Immunohistochemistry was performed for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 to compare the expression of these markers. For scoring of RBM3 expression, NF (nuclear staining fraction)×NI (nuclear staining intensity) was used. The RBM3 expression score was considered indicative of either low (≤4) or high (>4) expression. Western blot analysis was performed on breast cancer cell lines to evaluate RBM3 expression. RESULTS: Of the total 361 samples, 240 (66.5%) exhibited high RBM3 expression. High RBM3 expression was significantly associated with positivity for ER (p<0.001), PR (p<0.001), T stage (p<0.001), histologic grade (p<0.001), and % Ki-67 staining (p=0.004). Multivariate analysis revealed that high RBM3 expression was closely associated with prolonged disease-free survival (DFS) (p<0.001) and overall survival (OS) (p<0.001). Western blot analysis revealed reduced RBM3 expression in HCC1954 (HER2-enriched) and BT-20 (basal-like) cells with an aggressive phenotype. CONCLUSION: High nuclear RBM3 expression is strongly associated with a prolonged DFS and OS. Furthermore, RBM3 expression is closely associated with good prognostic markers such as ER and PR in IBC. High nuclear RBM3 expression is, therefore, a critical biomarker of favorable clinical outcomes in IBC.

Bile Granuloma Mimicking Peritoneal Seeding: A Case Report.

Laparoscopic cholecystectomy is a widely used treatment method for most cholelithiasis and is a relatively safe procedure. Foreign body granulomatous reaction to bile or gallstone spillage during laparoscopic cholecystectomy has rarely been reported. We report a case of bile granuloma after laparoscopic cholecystectomy, which mimicked peritoneal seeding. A 59-year-old Korean man presented with right upper quadrant pain. He underwent laparoscopic cholecystectomy for acute cholecystitis with cholelithiasis. Pathologic examination revealed an incidental adenocarcinoma invading the lamina propria with acute cholecystitis and cholelithiasis. After 3 months, follow-up abdominal computed tomography revealed a subhepatic nodule, which showed hypermetabolism on positron emission tomography-computed tomography. Suspecting localized peritoneal seeding, wedge resection of the liver, wedge resection of the transverse colon, and omentectomy were performed. Pathologic examination of the resected specimens revealed multiple bile granulomas. Awareness of bile granuloma mimicking malignancy is noteworthy for patient management to reduce unnecessary procedure during postoperative surveillance.

Diagnostic Accuracy of Combined Acetylcholinesterase Histochemistry and Calretinin Immunohistochemistry of Rectal Biopsy Specimens in Hirschsprung's Disease.

BACKGROUND: Acetylcholinesterase (AchE) histochemistry has been established as an accurate diagnostic tool for Hirschsprung's disease (HD). In addition, calretinin immunohistochemistry is also reported as a reliable and adjunctive method to diagnose HD. We investigated the diagnostic value of combined AchE histochemistry and calretinin immunohistochemistry in rectal suction biopsies from HD and non-HD patients. METHODS: We retrospectively reviewed 99 rectal suction biopsy specimens including 4 repeat biopsies from 95 patients (34 HD and 61 non-HD). Each specimen was evaluated with hematoxylin-eosin, AchE histochemistry, and calretinin immunohistochemistry. RESULTS: Of 95 patients, only 21 (22.1%) showed some ganglion cells. All 61 non-HD cases revealed no abnormal AchE-positive fibers. Of 34 HD patients, 32 exhibited abnormal AchE fibers, but 2 showed no stained fibers. None of the tissues from the HD patients exhibited calretinin immunoreactivity. Test sensitivity and specificity of AchE histochemistry alone were 93.5% and 100.0%, respectively, while calretinin immunohistochemistry were 100.0% and 85.2%, respectively. CONCLUSIONS: AchE histochemistry is a good diagnostic method for HD, if feasible, and a combination of AchE histochemistry and calretinin immunohistochemistry will help increase the accuracy of the diagnosis of HD.