Immunohistochemical analysis of 14-3-3 sigma and related proteins in hyperplastic and neoplastic breast lesions, with particular reference to early carcinogenesis

In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in breast carcinogenesis, we have studied the expression of 14-3-3sigma immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger protein (Efp) was also carried out. Immunohistochemically, expression of 14-3-3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERalpha. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested that it might be possible that CCHA is a precancerous lesion.     

基质金属蛋白酶9在宫颈柱状上皮异位及宫颈上皮内瘤变中不同表达的研究

目的 通过研究基质金属蛋白酶9（MMP-9）在宫颈柱状上皮异位、正常光滑宫颈及宫颈上皮内瘤变（CIN）组织中的不同表达,探讨三者癌变几率的不同及治疗的必要性.方法 对2007-2012年收治的30例宫颈柱状上皮异位、28例CIN、30例正常光滑宫颈组织石蜡标本,应用免疫组织化学方法检测MMP-9的表达.结果 宫颈柱状上皮异位组织MMP-9表达总阳性率23.3％（7/30）,正常光滑宫颈组织MMP-9表达总阳性率20.0％（6/30）,CIN组织MMP-9表达总阳性率96.4％（27/28）.宫颈柱状上皮异位组织和正常光滑宫颈组织MMP-9表达总阳性率均显著低于CIN组织,差异有统计学意义（P＜0.01）,而宫颈柱状上皮异位组织与正常光滑宫颈组织MMP-9表达总阳性率比较差异无统计学意义（P＞0.05）.结论 宫颈柱状上皮异位是一种生理表现,不应过度治疗.但生育年龄妇女应定期进行宫颈癌筛查.     

From the Cover: Rational design of helical architectures

Nature has mastered the art of creating complex structures through self-assembly of simpler building blocks. Adapting such a bottom-up view provides a potential route to the fabrication of novel materials. However, this approach suffers from the lack of a sufficiently detailed understanding of the noncovalent forces that hold the self-assembled structures together. Here we demonstrate that nature can indeed guide us, as we explore routes to helicity with achiral building blocks driven by the interplay between two competing length scales for the interactions, as in DNA. By characterizing global minima for clusters, we illustrate several realizations of helical architecture, the simplest one involving ellipsoids of revolution as building blocks. In particular, we show that axially symmetric soft discoids can self-assemble into helical columnar arrangements. Understanding the molecular origin of such spatial organisation has important implications for the rational design of materials with useful optoelectronic applications.     

An acoustic startle alters knee joint stiffness and neuromuscular control

Growing evidence suggests that the nervous system contributes to non‐contact knee ligament injury, but limited evidence has measured the effect of extrinsic events on joint stability. Following unanticipated events, the startle reflex leads to universal stiffening of the limbs, but no studies have investigated how an acoustic startle influences knee stiffness and muscle activation during a dynamic knee perturbation. Thirty‐six individuals were tested for knee stiffness and muscle activation of the quadriceps and hamstrings. Subjects were seated and instructed to resist a 40‐degree knee flexion perturbation from a relaxed state. During some trials, an acoustic startle (50 ms, 1000 Hz, 100 dB) was applied 100 ms prior to the perturbation. Knee stiffness, muscle amplitude, and timing were quantified across time, muscle, and startle conditions. The acoustic startle increased short‐range (no startle: 0.044 ± 0.011 N·m/deg/kg; average startle: 0.047 ± 0.01 N·m/deg/kg) and total knee stiffness (no startle: 0.036 ± 0.01 N·m/deg/kg; first startle 0.027 ± 0.02 N·m/deg/kg). Additionally, the startle contributed to decreased [vastus medialis (VM): 13.76 ± 33.6%; vastus lateralis (VL): 6.72 ± 37.4%] but earlier (VM: 0.133 ± 0.17 s; VL: 0.124 ± 0.17 s) activation of the quadriceps muscles. The results of this study indicate that the startle response can significantly disrupt knee stiffness regulation required to maintain joint stability. Further studies should explore the role of unanticipated events on unintentional injury.     

Lower esophageal palisade vessels and the definition of Barrett's esophagus

SUMMARY. The designated area of the columnar‐lined esophagus (CLE) is anatomically defined by the distal limit of the lower esophageal palisade vessels (LEPV) and the term ‘Barrett's esophagus’ is equally used along with the name CLE in Japan. The aim of this study was to investigate the actual prevalence of CLE based on the Japanese criteria and to evaluate the criteria per se. A total of 42 esophagi consecutively resected at this institute were included. All subjects underwent a surgical resection for squamous cell carcinoma of the esophagus. The position of the LEPV, squamocolumnar junction, the prevalence of CLE and intestinal metaplasia were investigated both pre‐ and postoperatively. Preoperative endoscopy revealed CLE based on the Japanese criteria in half of all patients. In the resected specimens the distal limit of LEPV was lower than the squamocolumnar junction in 95.2%. In other words, almost all cases had CLE (equivalent to Barrett's mucosa in Japanese criteria). However, most of the CLE areas were very short and their average maximum length was only about 5 mm. In addition, no intestinal metaplasia was observed in any of the CLE cases. Almost all individuals might therefore be diagnosed to have CLE or Barrett's mucosa based on precise endoscopic observations in Japan. The CLE located in a small area, e.g. less than 5 mm, defined according to the LEPV criteria without any other factor concerning typical Barrett's esophagus such as signs of gastroesophageal reflux should therefore be excluded from consideration as a high‐risk mucosa.     

Distribution and significance of the oesophageal and gastric cardiac mucosae: a study of 131 operation specimens

AIMS: To clarify the distribution and significance of the oesophageal and gastric cardiac mucosae at the oesophago-gastric junction (EGJ). METHODS AND RESULTS: Oesophagectomy specimens from 131 consecutive patients with middle and upper thoracic oesophageal cancer were examined. The surgically resected specimens including the EGJ were cut into 5 mm thick serial sections and examined histopathologically for the length of the oesophageal and gastric cardiac mucosae and the incidence of columnar epithelial islands (CEIs). We also determined the presence of short-segment Barrett's oesophagus (SSBE) and goblet cell metaplasia in SSBE. Oesophageal cardiac mucosa was found in 125 cases (95%) and gastric cardiac mucosa was found in all cases. The mean length of the oesophageal and gastric cardiac mucosa was 4 mm (range 1-26 mm) and 13 mm (range 2-64 mm), respectively. CEIs were found in 75 cases (57%). SSBE was found in 70 cases (53%), among which goblet cell metaplasia was found in 28 cases (21%). No long-segment Barrett's oesophagus was found. The mean length of oesophageal cardiac mucosa (6 mm) and gastric cardiac mucosa (17 mm) in SSBE was significantly greater than that (3 mm and 8 mm, respectively) in non-SSBE cases (P < 0.0001 and P < 0.0001). The incidence (69%) of CEIs in SSBE was significantly higher than that (44%) in non-SSBE cases (P = 0.005). CONCLUSIONS: Oesophageal and gastric cardiac mucosae were found frequently. Oesophageal cardiac glands and CEIs might play an important role in the development of SSBE.     

Flat epithelial atypia (DIN 1a, atypical columnar change): an underdiagnosed entity very frequently coexisting with lobular neoplasia

AIMS: Flat epithelial atypia of the breast [FEA; synonyms: ductal intraepithelial neoplasia (DIN) 1a, atypical columnar change] is increasingly recognized by pathologists and shows distinct genetic alterations. The aim of this study was to determine its biological significance as an incidental finding in breast biopsy specimens. METHODS AND RESULTS: On the assumption that both FEA and lobular neoplasia (LN) derive from progenitor cells in the terminal ductal-lobular unit, we investigated the association between FEA and LN semiquantitatively in 111 excisional breast biopsy specimens which contained LN, but did not contain ductal carcinoma in situ (DCIS) or invasive carcinoma. Ninety-six cases (86.5%) revealed coexistence of LN and FEA (P < 0001). The distribution of LN was focal in 41 cases (37%), multifocal in 50 (45%) and extensive in 20 (18%) cases. FEA was identified as focal, multifocal and extensive in 29 (26%), 42 (38%) and 25 (23%) cases, respectively. Distribution patterns of LN and FEA showed no statistically significant correlation. CONCLUSIONS: Due to the striking association between LN and FEA in our material, one may speculate that these two lesions are biologically related and that FEA is an early but non-obligate precursor lesion similar to LN. Based on this assumption, regular clinical and mammographic follow-up of patients with FEA would be prudent.