Esophageal SCC

Wieder et al. [80] evaluated the time course of therapy-induced changes in tumor glucose metabolism during chemoradiotherapy of esophageal SCC in a cohort of 38 patients. Early metabolic response, defined as a reduction of baseline SUV of more than 30%, predicted histopathologic response 2 weeks after induction of chemotherapy with a sensitivity of 93% and a specificity of 88%, respectively. Changes in tumor metabolic activity early in the time course of preoperative chemoradiotherapy were also significantly correlated with patient survival (p < 0.011). 

Primary pulmonary SCC can occasionally be distinguished from esophageal SCC with TTF-1. Although both neoplasms are usually nonreactive, occasional pulmonary squamous cell carcinomas may show extensive and strong nuclear TTF-1 staining, whereas esophageal SCCs are consistently negative for TTF-1. 

Distinction between SCC and thymic carcinoma is also occasionally required. CD5 can be diffusely and strongly positive in primary thymic carcinoma and nonreactive in esophageal SCCs. Importantly, selective CD5 reactivity of thymic carcinomas is highly dependent on the pTI of the antigen retrieval solution and the antibody clone. Some CD5 antibodies diffusely and strongly stain both thymic carcinomas and esophageal squamous carcinomas. 79... 

Mesothelioma can occasionally be morphologically and clinically similar to poorly differentiated, nonkeratinizing, primary esophageal SCC. Both neoplasms are immunoreactive with calretinin and CK5/6, leaving WTl as the single positive diagnostic marker for mesothelioma. ... 

Cyclins, eyehn-dependent kinases (CDKs), and CDK inhibitors play important roles in eontroUing major cheekpoints in the mammalian cell cycle (Matsumoto et al. 1999). In the cell cycle, the transition from G1 phase to S phase is believed to be the most important checkpoint (Hunter and Pines 1994). We previously found that in esophageal SCCs, G1 phase eyclin, cyclin Dl, its catalytic partner, CDK4, and CDK inhibitors such as p27 and p57 could contribute to tumor progression (Matsumoto et al. 1999 Ishikawa et al. 1998 Anayama et al. 1998 Matsumoto et al. 2000). 

Moreover, further mutation of p53 may oecur in the presenee of high NO levels (Lala and Qiakraborty 2001). A positive eorrelation between total NOS aetivity and frequeney of p53 mutation was reported for eoloieetal eaneer and lung adenoearei-noma the predominant mutation was G C to T A transversion at CpG dinueleotides in the former study, and the G C to A T transition in the latter (Ambs et al. 1999 Fujimoto et al. 1998). In esophageal SCC, however, we failed to find a signifieant relationship between iNOS expression and type of p53 mutation (Matsumoto et al. 2003). 

Fig. 18.2 Cumulative Kaplan-Meier survival curves for patients with esophageal SCCs divided by iNOS immunoreactivity...

ADENOID CYSTIC CARCINOMA Most reported esophageal adenoid cystic carcinomas are basaloid SCCs true adenoid cystic carcinomas of the esophagus are extremely rare. Esophageal salivary gland-type adenoid cystic carcinomas stain diffusely and strongly with CAM5.2 and AE1/AE3. 34bE12 and CEA stain the ductal-type cells, whereas S-100, actin, and vimentin stain the basaloid-type cells. 

Immunophenotypically, NETs stain diffusely and strongly with synaptophysin and chromogranin, whereas high-grade, large cell carcinomas may only be positive for synaptophysin. Small cell carcinomas that arise in association with SCC may express CEA, and up to one half of esophageal small cell carcinomas may be immunoreactive with XTF-l. °79i... 

ALA, Aminolevulinic acid ALT, aspartate aminotransferase HpD, hematoporphyrin derivative mTHPC, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin SCC, Squamous cell carcinoma TOP, tracheo esophageal fistula Tl, cancer involving the mucosa and/or submucosa T2, cancer invading into muscularis propria but not through this layer. Indicates number of tumors. 

In the last 20 years there has been a dramatic increase in the incidence of esophageal adenocarcinoma (EAC) in the Western world. EAC is now more commonly encountered in the West than SCC of the esophagus (Figure 11.1). Several studies have documented this trend. Surgical series from 1926 to 1976 reported that EAC was uncommon (0.8 to 3.7% of esophageal cancers). Recent smgical series from major referral institutions showed 60 to 80% of patients with esophageal cancer had adenocarcinomas (compared with 10 to 15% about 10 years ago). ... 

A recent study by Freedman et al. noted a moderately increased risk of EAC in patients who underwent cholecystectomy (CCK). There was no association of CCK with see of the esophagus. Patients with gallstone disease, who did not undergo CCK, did not have an increased incidence of EAC or SCC of the esophagus. It is postulated that after CCK, patients have increased reflux of bile and pancreatic juice from the duodenum to the stomach. This then reaches the esophageal mucosa, on which it has a toxic effect. Such toxic effects can predispose to the formation of EAC. Further studies are needed to identify a link between bile reflux and EAC. 

External beam radiation used as sole therapy or in combination with 5-fluorouracil (5 FU) can be used to relieve dysphagia in over two-thirds of patients with SCC. Symptoms recur, however, due to recurrent cancer or fibrotic strictures. The most effective chemotherapeutic regimen in advanced esophageal cancer is epirubicin, cisplatin, and continuous infusion of 5 FU. Two-thirds of cases respond with improvement of dysphagia. ... 

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