Effect of sex hormones on extracellular matrix of lamina propria in rat vocal fold.

OBJECTIVES: The role of sex hormones for voice changes in men and women is presently unknown. To determine the effect of sex hormone on the vocal fold, changes of the extracellular matrix (ECM) in vocal fold lamina propria were assessed in orchiectomized (ORX) and ovariectomized (OVX) rats. METHODS: Male and female Sprague-Dawley rats were divided into sham-operated control male (CON-ORX), ORX, sham-operated female (CON-OVX), and OVX rats. Histological changes and expression of ECM-related genes in lamina propria of the vocal fold were evaluated at 4 and 12 weeks after surgery. RESULTS: Testosterone and estradiol levels decreased in the ORX and OVX groups, respectively. ORX groups did not have significant changes compared with CON-ORX groups. However, the expression of hyaluronic acid (HA) was decreased in the OVX group compared with the CON-OVX group. The expression of collagen I in OVX was lower than in the CON-OVX group. Collagen III levels were elevated at 4 weeks in the OVX group, but collagen III levels were diminished at 12 weeks in the OVX group. Expression of elastin in the ECM was less dense in the OVX group compared with controls. The expression MMP-1 and MMP-9 showed significantly increase in the OVX group compared to the CON-OVX group. CONCLUSION: No changes of the ECM-related genes in the vocal fold lamina propria were observed in ORX groups with reduced testosterone. However, changes of several ECM-related genes were observed in OVX groups with decreased estrogen. These results indicate that the vocal fold is an estrogen-sensitive target organ and that decreased estrogen, not testosterone, can affect the expression of several ECM-related molecules of vocal fold. LEVEL OF EVIDENCE: NA Laryngoscope, 130:732-740, 2020.

Clinicopathologic features of early gastric carcinoma with lymphoid stroma and feasibility of endoscopic submucosal dissection.

BACKGROUND: Gastric carcinoma with lymphoid stroma (GCLS) is a rare disease known to have unique features and a favorable prognosis. This study aimed to determine the clinicopathologic features of early GCLS (EGCLS) and define the feasibility of endoscopic submucosal dissection (ESD) for EGCLS. METHODS: We performed a retrospective analysis of 70 EGCLS patients treated via ESD or surgery and 1626 patients who underwent surgical resection for early non-GCLS (ENGCLS) between January 2007 and December 2014 at Pusan National University Hospital, Busan, Republic of Korea. RESULTS: The mean age of EGCLS patients was 58 years (range 36-77 years); a male predominance (3.7:1) was observed, and 81.4% showed Epstein-Barr virus positivity. Compared with ENGCLS, EGCLS was macroscopically more elevated (34.3 vs. 18.0%, P = 0.003) and located more proximally (upper third: 37.1 vs. 9.7%, P < 0.001). Tumor size was smaller (2.1 ± 1.1 vs. 3.1 ± 2.0 cm, P < 0.001), but submucosal invasion was more frequent (77.1 vs. 44.4%, P < 0.001) and deeper in the EGCLS group. Among the 59 EGCLS patients who were treated surgically, only two (3.4%) showed lymph node metastasis (LNM). Despite submucosal invasion, EGCLS showed a lower LNM rate (4.0 vs. 19.4%, P = 0.007) than ENGCLS, even in patients with SM3 EGCLS (5.3 vs. 24.5%, P = 0.007). There were no recurrences in the available ten patients who underwent ESD alone during a mean follow-up of 37.2 months. CONCLUSIONS: In this study, we observed unique clinicopathologic features with a very low LNM rate in EGCLS. We consider ESD a potentially curative treatment strategy for EGCLS despite deep submucosal invasion, especially in patients with poor performance status and significant comorbidities.

Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancers.

PURPOSE: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)-positive breast cancers. MATERIALS AND METHODS: Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR-/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin-stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray. RESULTS: MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR-/HER2+ breast cancers. However, MxA was not a prognostic factor. CONCLUSION: High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

Venous Invasion in Colorectal Cancer: Impact of Morphologic Findings on Detection Rate.

PURPOSE: Venous invasion (VI) is widely accepted as a poor prognostic factor in colorectal cancer (CRC), and is indicated as a high-risk factor determining the use of adjuvant chemotherapy in CRC. However, there is marked interobserver and intraobserver variability in VI identification and marked variability in the real prevalence of VI in CRC. MATERIALS AND METHODS: We investigated the detection rate of VI in 93 consecutive cases of T3 or T4 CRC based on the following: original pathology report, review of hematoxylin and eosin (H&E) slides with attention to the "protruding tongue" and "orphan arteriole" signs, and elastic stain as the gold standard. RESULTS: Overall, the detection rate of VI was significantly increased as follows: 14/93 (15.1%) in the original pathology report, 38/93 (40.9%) in review of H&E slides with attention to the "protruding tongue" and "orphan arteriole" signs, and 45/93 (48.4%) using elastic stain. VI detection based on morphologic features showed 77.8% sensitivity and 91.1% specificity and showed a linear correlation (Spearman correlation coefficient, 0.727; p < 0.001) with VI detected by elastic stain. In addition, improved agreement between detection methods (detection on the basis of morphologic features, κ=0.719 vs. original pathology report, κ=0.318) was observed using kappa statistics. CONCLUSION: Slide review with special attention to the "protruding tongue" and "orphan arteriole" signs could be used for better identification of VI in CRC in routine surgical practice.

Gastric crypt dysplasia: a distinct subtype of gastric dysplasia with characteristic endoscopic features and immunophenotypic and biological anomalies.

AIMS: Previous reports have shown that gastric epithelial dysplasia (GED) limited to the crypt (gastric crypt dysplasia, GCD) is commonly identified at the periphery of gastric carcinoma. However, it is unknown whether GCD is endoscopically identifiable, and how it relates to classic GED lesions. METHODS AND RESULTS: We investigated 1196 consecutive endoscopic resections of GED lesions between January 2011 and December 2014. We also evaluated clinicopathological features of these lesions, as well as the immunohistochemical expression of mucin (Muc)2, Muc5AC, Muc6, CD10, Ki67 and p53. We found 51 (4.3%) lesions composed microscopically of GCD among 1196 GED lesions. Those were elevated mucosal lesions (66.7%) similar in colour and texture to the adjacent mucosa (68.6%). GCD was likely to have an antropyloric location and a higher grade than the adenomatous type, similar to the foveolar and hybrid types (P < 0.05). A gastric immunophenotype was more common in GCD compared to adenomatous GED (P < 0.05). Ki-67- and p53-positive cells were more evident in GCD compared to the adjacent gastric mucosa. CONCLUSIONS: Our results demonstrated that GCD can be an endoscopically identifiable lesion, sharing many similarities with foveolar and hybrid GED, for which it may represent a precursor lesion in the gastric carcinogenic sequence.